SEARCH

SEARCH BY CITATION

References

  • 1
    Davies, H., G. R. Bignell, C. Cox, P. Stephens, S. Edkins, S. Clegg, J. Teague, H. Woffendin, M. J. Garnett, W. Bottomley, N. Davis, E. Dicks, R. Ewing, Y. Floyd, K. Gray, S. Hall, R. Hawes, J. Hughes, V. Kosmidou, A. Menzies, C. Mould, A. Parker, C. Stevens, S. Watt, S. Hooper, R. Wilson, H. Jayatilake, B. A. Gusterson, C. Cooper, J. Shipley, D. Hargrave, K. Pritchard-Jones, N. Maitland, G. Chenevix-Trench, G. J. Riggins, D. D. Bigner, G. Palmieri, A. Cossu, A. Flanagan, A. Nicholson, J. W. Ho, S. Y. Leung, S. T. Yuen, B. L. Weber, H. F. Seigler, T. L. Darrow, H. Paterson, R. Marais, C. J. Marshall, R. Wooster, M. R. Stratton and P. A. Futreal (2002) Mutations of the B-Raf gene in human cancer. Nature 417, 949954.
  • 2
    Van Elsas, A., S. Zerp, S. Van Der Flier, M. Kruse-Wolters, A. Vacca, D. J. Ruiter and P. Schrier (1995) Analysis of N-ras mutations in human cutaneous melanoma: Tumor heterogeneity detected by polymerase chain reaction/single-stranded conformation polymorphism analysis. Recent Results Cancer Res. 139, 5767.
  • 3
    Omholt, K., A. Platz, L. Kanter, U. Ringborg and J. Hansson (2003) N-Ras and B-Raf mutations arise early during melanoma pathogenesis and are preserved throughout tumor progression. Clin. Cancer Res. 9, 64836488.
  • 4
    Vojtek, A. B. and C. J. Der (1998) Increasing complexity of the Ras signaling pathway. J. Biol. Chem. 273, 1992519928.
  • 5
    Carr, J. and R. M. MacKie (1994) Point mutations in the N-Ras oncogene in malignant melanoma and congenital naevi. Br. J. Dermatol. 131, 7277.
  • 6
    Pollock, P. M., U. L. Harper, K. S. Hansen, L. M. Yudt, M. Stark, C. M. Robbins, T. Y. Moses, G. Hostetter, U. Wagner, J. Kakareka, G. Salem, T. Pohida, P. Heenan, P. Duray, O. Kallioniemi, N. K. Hayward, J. M. Trent and P. S. Meltzer (2003) High frequency of B-Raf mutations in nevi. Nat. Genet. 33, 1920.
  • 7
    Gorden, A., I. Osman, W. Gai, D. He, W. Huang, A. Davidson, A. N. Houghton, K. Busam and D. Polsky (2003) Analysis of B-Raf and N-Ras mutations in metastatic melanoma tissues. Cancer Res. 63, 39553957.
  • 8
    Kumar, R., S. Angelini, K. Czene, I. Sauroja, M. Hahka-Kemppinen, S. Pyrhonen and K. Hemminki (2003) B-Raf mutations in metastatic melanoma: A possible association with clinical outcome. Clin. Cancer Res. 9, 33623368.
  • 9
    Ball, N. J., J. J. Yohn, J. G. Morelli, D. A. Norris, L. E. Golitz and J. P. Hoeffler (1994) Ras mutations in human melanoma: A marker of malignant progression. J. Invest. Dermatol. 102, 285290.
  • 10
    Satyamoorthy, K., G. Li, M. R. Gerrero, M. S. Brose, P. Volpe, B. L. Weber, P. Van Belle, D. E. Elder and M. Herlyn (2003) Constitutive mitogen-activated protein kinase activation in melanoma is mediated by both B-Raf mutations and autocrine growth factor stimulation. Cancer Res. 63, 756759.
  • 11
    Smalley, K. S. (2003) A pivotal role for ERK in the oncogenic behaviour of malignant melanoma? Int. J. Cancer 104, 527532.
  • 12
    Collisson, E. A., A. De, H. Suzuki, S. S. Gambhir and M. S. Kolodney (2003) Treatment of metastatic melanoma with an orally available inhibitor of the Ras-Raf-MAPK cascade. Cancer Res. 63, 56695673.
  • 13
    Karasarides, M., A. Chiloeches, R. Hayward, D. Niculescu-Duvaz, I. Scanlon, F. Friedlos, L. Ogilvie, D. Hedley, J. Martin, C. J. Marshall, C. J. Springer and R. Marais (2004) B-Raf is a therapeutic target in melanoma. Oncogene 23, 62926298.
  • 14
    Hingorani, S. R., M. A. Jacobetz, G. P. Robertson, M. Herlyn and D. A. Tuveson (2003) Suppression of B-Raf(V599E) in human melanoma abrogates transformation. Cancer Res. 63, 51985202.
  • 15
    Sumimoto, H., M. Miyagishi, H. Miyoshi, S. Yamagata, A. Shimizu, K. Taira and Y. Kawakami (2004) Inhibition of growth and invasive ability of melanoma by inactivation of mutated B-Raf with lentivirus-mediated RNA interference. Oncogene 23, 60316039.
  • 16
    Houben, R., J. C. Becker, A. Kappel, P. Terheyden, E. B. Brocker, R. Goetz and U. R. Rapp (2004) Constitutive activation of the Ras-Raf signaling pathway in metastatic melanoma is associated with poor prognosis. J. Carcinog. 3, 6.
  • 17
    Akslen, L. A., S. Angelini, O. Straume, I. M. Bachmann, A. Molven, K. Hemminki and R. Kumar (2005) B-Raf and N-Ras mutations are frequent in nodular melanoma but are not associated with tumor cell proliferation or patient survival. J. Invest. Dermatol. 125, 312317.
  • 18
    Chang, D. Z., K. S. Panageas, I. Osman, D. Polsky, K. Busam and P. B. Chapman (2004) Clinical significance of B-Raf mutations in metastatic melanoma. J. Transl. Med. 2, 46.
  • 19
    Poynter, J. N., J. T. Elder, D. R. Fullen, R. P. Nair, M. S. Soengas, T. M. Johnson, B. Redman, N. E. Thomas and S. B. Gruber (2006) B-Raf and N-Ras mutations in melanoma and melanocytic nevi. Melanoma Res. 16, 267273.
  • 20
    Takayama, T., M. Ohi, T. Hayashi, K. Miyanishi, A. Nobuoka, T. Nakajima, T. Satoh, R. Takimoto, J. Kato, S. Sakamaki and Y. Niitsu (2001) Analysis of K-ras, APC, and β-catenin in aberrant crypt foci in sporadic adenoma, cancer, and familial adenomatous polyposis. Gastroenterology 121, 599611.
  • 21
    Yamashita, N., T. Minamoto, A. Ochiai, M. Onda and H. Esumi (1995) Frequent and characteristic K-Ras activation and absence of p53 protein accumulation in aberrant crypt foci of the colon. Gastroenterology 108, 434440.
  • 22
    Michaloglou, C., L. C. Vredeveld, M. S. Soengas, C. Denoyelle, T. Kuilman, C. M. Van Der Horst, D. M. Majoor, J. W. Shay, W. J. Mooi and D. S. Peeper (2005) B-RafE600-associated senescence-like cell cycle arrest of human naevi. Nature 436, 720724.
  • 23
    Tsao, H., X. Zhang, K. Fowlkes and F. G. Haluska (2000) Relative reciprocity of N-Ras and PTEN/MMAC1 alterations in cutaneous melanoma cell lines. Cancer Res. 60, 18001804.
  • 24
    Daniotti, M., M. Oggionni, T. Ranzani, V. Vallacchi, V. Campi, D. Di Stasi, G. D. Torre, F. Perrone, C. Luoni, S. Suardi, M. Frattini, S. Pilotti, A. Anichini, G. Tragni, G. Parmiani, M. A. Pierotti and M. Rodolfo (2004) B-Raf alterations are associated with complex mutational profiles in malignant melanoma. Oncogene 23, 59685977.
  • 25
    Tomicic, J. and H. J. Wanebo (2003) Mucosal melanomas. Surg. Clin. North Am. 83, 237252.
  • 26
    Rivers, J. K. (2004) Is there more than one road to melanoma? Lancet 363, 728730.
  • 27
    Saldanha, G., D. Purnell, A. Fletcher, L. Potter, A. Gillies and J. H. Pringle (2004) High B-Raf mutation frequency does not characterize all melanocytic tumor types. Int. J. Cancer 111, 705710.
  • 28
    Cohen, Y., N. Goldenberg-Cohen, P. Parrella, I. Chowers, S. L. Merbs, J. Pe’er and D. Sidransky (2003) Lack of B-Raf mutation in primary uveal melanoma. Invest. Ophthalmol. Vis. Sci. 44, 28762878.
  • 29
    Edmunds, S. C., I. A. Cree, F. Di Nicolantonio, J. L. Hungerford, J. S. Hurren and D. P. Kelsell (2003) Absence of B-Raf gene mutations in uveal melanomas in contrast to cutaneous melanomas. Br. J. Cancer 88, 14031405.
  • 30
    Edwards, R. H., M. R. Ward, H. Wu, C. A. Medina, M. S. Brose, P. Volpe, S. Nussen-Lee, H. M. Haupt, A. M. Martin, M. Herlyn, S. R. Lessin and B. L. Weber (2004) Absence of B-Raf mutations in UV-protected mucosal melanomas. J. Med. Genet. 41, 270272.
  • 31
    Kilic, E., H. T. Bruggenwirth, M. M. Verbiest, E. C. Zwarthoff, N. M. Mooy, G. P. Luyten and A. De Klein (2004) The Ras-B-Raf kinase pathway is not involved in uveal melanoma. Melanoma Res. 14, 203205.
  • 32
    Shields, J. M., N. E. Thomas, M. Cregger, A. J. Berger, M. Leslie, C. Torrice, H. Hao, S. Penland, J. Arbiser, G. Scott, T. Zhou, M. Bar-Eli, J. E. Bear, C. J. Der, W. K. Kaufmann, D. L. Rimm and N. E. Sharpless (2007) Lack of extracellular signal-regulated kinase mitogen-activated protein kinase signaling shows a new type of melanoma. Cancer Res. 67, 15021512.
  • 33
    Pavey, S., P. Johansson, L. Packer, J. Taylor, M. Stark, P. M. Pollock, G. J. Walker, G. M. Boyle, U. Harper, S. J. Cozzi, K. Hansen, L. Yudt, C. Schmidt, P. Hersey, K. A. Ellem, M. G. O’Rourke, P. G. Parsons, P. Meltzer, M. Ringner and N. K. Hayward (2004) Microarray expression profiling in melanoma reveals a B-Raf mutation signature. Oncogene 23, 40604067.
  • 34
    Johansson, P., S. Pavey and N. Hayward (2007) Confirmation of a B-Raf mutation-associated gene expression signature in melanoma. Pigment Cell Res. 20, 216221.
  • 35
    Kortylewski, M., P. C. Heinrich, M. E. Kauffmann, M. Bohm, A. MacKiewicz and I. Behrmann (2001) Mitogen-activated protein kinases control p27/Kip1 expression and growth of human melanoma cells. Biochem. J. 357, 297303.
  • 36
    Lefevre, G., A. Calipel, F. Mouriaux, C. Hecquet, F. Malecaze and F. Mascarelli (2003) Opposite long-term regulation of c-Myc and p27Kip1 through overactivation of Raf-1 and the MEK/ERK module in proliferating human choroidal melanoma cells. Oncogene 22, 88138822.
  • 37
    Bhatt, K. V., R. Hu, L. S. Spofford and A. E. Aplin (2007) Mutant B-Raf signaling and cyclin D1 regulate Cks1/S-phase kinase-associated protein 2-mediated degradation of p27Kip1 in human melanoma cells. Oncogene 26, 10561066.
  • 38
    Sumimoto, H., K. Hirata, S. Yamagata, H. Miyoshi, M. Miyagishi, K. Taira and Y. Kawakami (2006) Effective inhibition of cell growth and invasion of melanoma by combined suppression of B-Raf (V599E) and Skp2 with lentiviral RNAi. Int. J. Cancer 118, 472476.
  • 39
    Goodall, J., C. Wellbrock, T. J. Dexter, K. Roberts, R. Marais and C. R. Goding (2004) The Brn-2 transcription factor activated B-Raf to melanoma proliferation. Mol. Cell. Biol. 24, 29242932.
  • 40
    Lopez-Bergami, P., C. Huang, J. S. Goydos, D. Yip, M. Bar-Eli, M. Herlyn, K. S. Smalley, A. Mahale, A. Eroshkin, S. Aaronson and Z. Ronai (2007) Rewired ERK-JNK signaling pathways in melanoma. Cancer Cell 11, 447460.
  • 41
    Goding, C. R. (2000) Mitf from neural crest to melanoma: Signal transduction and transcription in the melanocyte lineage. Genes Dev. 14, 17121728.
  • 42
    Wu, M., T. J. Hemesath, C. M. Takemoto, M. A. Horstmann, A. G. Wells, E. R. Price, D. Z. Fisher and D. E. Fisher (2000) c-Kit triggers dual phosphorylations, which couple activation and degradation of the essential melanocyte factor Mi. Genes Dev. 14, 301312.
  • 43
    Kim, D.-S., E.-S. Hwang, J.-E. Lee, S.-Y. Kim, S.-B. Kwon and K.-C. Park (2003) Sphingosine-1-phosphate decreases melanin synthesis via sustained ERK activation and subsequent MITF degradation. J. Cell Sci. 116, 16991706.
  • 44
    Eisenmann, K. M., M. W. VanBrocklin, N. A. Staffend, S. M. Kitchen and H.-M. Koo (2003) Mitogen-activated protein kinase pathway-dependent tumor-specific survival signaling in melanoma cells through inactivation of the proapoptotic protein Bad. Cancer Res. 63, 83308337.
  • 45
    Krasilnikov, M., V. N. Ivanov, J. Dong and Z. Ronai (2003) ERK and PI3K negatively regulate STAT-transcriptional activities in human melanoma cells: Implications towards sensitization to apoptosis. Oncogene 22, 40924101.
  • 46
    Aguirre Ghiso, J. A., K. Kovalski and L. Ossowski (1999) Tumor dormancy induced by downregulation of urokinase receptor in human carcinoma involves integrin and MAPK signaling. J. Cell Biol. 147, 89104.
  • 47
    Santibanez, J. F., M. Iglesias, P. Frontelo, J. Martinez and M. Quintanilla (2000) Involvement of the Ras/MAPK signaling pathway in the modulation of urokinase production and cellular invasiveness by transforming growth factor-β(1) in transformed keratinocytes. Biochem. Biophys. Res. Commun. 273, 521527.
  • 48
    Genersch, E., K. Hayess, Y. Neuenfeld and H. Haller (2000) Sustained ERK phosphorylation is necessary but not sufficient for MMP-9 regulation in endothelial cells: Involvement of Ras-dependent and -independent pathways. J. Cell Sci. 113, 43194330.
  • 49
    Tower, G. B., C. C. Coon, U. Benbow, M. P. Vincenti and C. E. Brinckerhoff (2002). ERK 1/2 differentially regulates the expression from the 1G/2G single nucleotide polymorphism in the MMP-1 promoter in melanoma cells. Biochim. Biophys. Acta 1586, 265274.
  • 50
    Ishii, Y., T. Ogura, M. Tatemichi, H. Fujisawa, F. Otsuka and H. Esumi (2003) Induction of matrix metalloproteinase gene transcription by nitric oxide and mechanisms of MMP-1 gene induction in human melanoma cell lines. Int. J. Cancer 103, 161168.
  • 51
    Ramos, M. C., H. Steinbrenner, D. Stuhlmann, H. Sies and P. Brenneisen (2004) Induction of MMP-10 and MMP-1 in a squamous cell carcinoma cell line by ultraviolet radiation. Biol. Chem. 385, 7586.
  • 52
    Huntington, J. T., J. M. Shields, C. J. Der, C. A. Wyatt, U. Benbow, C. L. Slingluff Jr and C. E. Brinckerhoff (2004) Overexpression of collagenase 1 (MMP-1) is mediated by the ERK pathway in invasive melanoma cells: Role of B-Raf mutation and fibroblast growth factor signaling. J. Biol. Chem. 279, 3316833176.
  • 53
    Woods, D., H. Cherwinski, E. Venetsanakos, A. Bhat, S. Gysin, M. Humbert, P. F. Bray, V. L. Saylor and M. McMahon (2001) Induction of {β}3-integrin gene expression by sustained activation of the Ras-regulated Raf-MEK-extracellular signal-regulated kinase signaling pathway. Mol. Cell. Biol. 21, 31923205.
  • 54
    Sumimoto, H., F. Imabayashi, T. Iwata and Y. Kawakami (2006) The B-Raf-MAPK signaling pathway is essential for cancer-immune evasion in human melanoma cells. J. Exp. Med. 203, 16511656.
  • 55
    Haluska, F. G., H. Tsao, H. Wu, F. S. Haluska, A. Lazar and V. Goel (2006) Genetic alterations in signaling pathways in melanoma. Clin. Cancer Res. 12, 2301s2307s.
  • 56
    Sosman, J. A. and I. Puzanov (2006) Molecular targets in melanoma from angiogenesis to apoptosis. Clin. Cancer Res. 12, 2376s2383s.
  • 57
    Hoeflich, K. P., D. C. Gray, M. T. Eby, J. Y. Tien, L. Wong, J. Bower, A. Gogineni, J. Zha, M. J. Cole, H. M. Stern, L. J. Murray, D. P. Davis and S. Seshagiri (2006) Oncogenic B-Raf is required for tumor growth and maintenance in melanoma models. Cancer Res. 66, 9991006.
  • 58
    Wang, J. Y., K. M. Wilcoxen, K. Nomoto and S. Wu (2007) Recent advances of MEK inhibitors and their clinical progress. Curr. Top. Med. Chem. 7, 13641378.
  • 59
    Li, N., D. Batt and M. Warmuth (2007) B-Raf kinase inhibitors for cancer treatment. Curr. Opin. Investig. Drugs 8, 452456.
  • 60
    Sharma, A., M. A. Tran, S. Liang, A. K. Sharma, S. Amin, C. D. Smith, C. Dong and G. P. Robertson (2006) Targeting mitogen-activated protein kinase/extracellular signal-regulated kinase kinase in the mutant (V600E) B-Raf signaling cascade effectively inhibits melanoma lung metastases. Cancer Res. 66, 82008209.
  • 61
    Smalley, K. S. M., N. K. Haass, P. A. Brafford, M. Lioni, K. T. Flaherty and M. Herlyn (2006) Multiple signaling pathways must be targeted to overcome drug resistance in cell lines derived from melanoma metastases. Mol. Cancer Ther. 5, 11361144.
  • 62
    Meier, F., S. Busch, K. Lasithiotakis, D. Kulms, C. Garbe, E. Maczey, M. Herlyn and B. Schittek (2007) Combined targeting of MAPK and Akt signalling pathways is a promising strategy for melanoma treatment. Br. J. Dermatol. 156, 12041213.
  • 63
    Steelman, L. S., F. E. Bertrand and J. A. McCubrey (2004) The complexity of PTEN: Mutation, marker and potential target for therapeutic intervention. Expert. Opin. Ther. Targets 8, 537550.
  • 64
    Parmiter, A. H., G. Balaban, W. H. Clark Jr and P. C. Nowell (1988) Possible involvement of the chromosome region 10q24–q26 in early stages of melanocytic neoplasia. Cancer Genet. Cytogenet. 30, 313317.
  • 65
    Herbst, R. A., J. Weiss, A. Ehnis, W. K. Cavenee and K. C. Arden (1994) Loss of heterozygosity for 10q22-10qter in malignant melanoma progression. Cancer Res. 54, 31113114.
  • 66
    Healy, E., I. Rehman, B. Angus and J. L. Rees (1995) Loss of heterozygosity in sporadic primary cutaneous melanoma. Genes Chromosomes Cancer 12, 152156.
  • 67
    Simpson, L. and R. Parsons (2003) PTEN: Life as a tumor suppressor. Exp. Cell Res. 264, 2941.
  • 68
    Wu, H., V. Goel and F. G. Haluska (2003) PTEN signaling pathways in melanoma. Oncogene 22, 31133122.
  • 69
    Guldberg, P., P. Thor Straten, A. Birck, V. Ahrenkiel, A. F. Kirkin and J. Zeuthen (1997) Disruption of the MMAC1/PTEN gene by deletion or mutation is a frequent event in malignant melanoma. Cancer Res. 57, 36603663.
  • 70
    Tsao, H., X. Zhang, E. Benoit and F. G. Haluska (1998) Identification of PTEN/MMAC1 alterations in uncultured melanomas and melanoma cell lines. Oncogene 16, 33973402.
  • 71
    Birck, A., V. Ahrenkiel, J. Zeuthen, K. Hou-Jensen and P. Guldberg (2000) Mutation and allelic loss of the PTEN/MMAC1 gene in primary and metastatic melanoma biopsies. J. Invest. Dermatol. 114, 277280.
  • 72
    Reifenberger, J., M. Wolter, J. Boström, K. Schulte, T. Ruzicka and G. Reifenberger (2000) Allelic losses on chromosome arm 10q and mutation of the PTEN (MMAC1) tumour suppressor gene in primary and metastatic malignant melanomas. Virchows Arch. 436, 487493.
  • 73
    Celebi, J. T., I. Shendrik, D. N. Silvers and M. J. Peacocke (2000) Identification of PTEN mutations in metastatic melanoma specimens. J. Med. Genet. 37, 653657.
  • 74
    Zhou, X. P., O. Gimm, H. Hampel, T. Niemann, M. J. Walker and C. Eng (2000) Epigenetic PTEN silencing in malignant melanomas without PTEN mutation. Am. J. Pathol. 157, 11231128.
  • 75
    Dahia, P. L. M., D. J. Marsh, Z. Zheng, J. Zedenius, P. Komminoth, T. Frisk, G. Wallin, R. Parsons, M. Longy, C. Larsson and C. Eng (1997) Somatic deletions and mutations in the Cowden disease gene, PTEN, in sporadic thyroid tumors. Cancer Res. 57, 47104713.
  • 76
    Whang, Y. E., X. Wu, H. Suzuki, R. E. Reiter, C. Tran, R. L. Vessella, J. W. Said, W. B. Isaacs and C. L. Sawyers (1998) Inactivation of the tumor suppressor PTEN/MMAC1 in advanced human prostate cancer through loss of expression. Proc. Natl Acad. Sci. USA 95, 52465250.
  • 77
    Salvesen, H. B., N. MacDonald, A. Ryan, I. J. Jacobs, E. D. Lynch, L. A. Akslen and S. Das (2001) PTEN methylation is associated with advanced stage and microsatellite instability in endometrial carcinoma. Int. J. Cancer 91, 2226.
  • 78
    Mirmohammadsadegh, A., A. Marini, S. Nambiar, M. Hassan, A. Tannapfel, T. Ruzicka and U. R. Hengge (2006) Epigenetic silencing of the PTEN gene in melanoma. Cancer Res. 66, 65466552.
  • 79
    Whiteman, D. C., X. P. Zhou, M. C. Cummings, S. Pavey, N. K. Hayward and C. Eng (2002) Nuclear PTEN expression and clinicopathologic features in a population-based series of primary cutaneous melanoma. Int. J. Cancer 99, 6367.
  • 80
    Wang, X., L. C. Trotman, T. Koppie, A. Alimonti, Z. Chen, Z. Gao, J. Wang, H. Erdjument-Bromage, P. Tempst, C. Cordon-Cardo, P. P. Pandolfi and X. Jiang (2007) NEDD4-1 is a proto-oncogenic ubiquitin ligase for PTEN. Cell 128, 129139.
  • 81
    Robertson, G. P., F. B. Furnari, M. E. Miele, M. J. Glendening, D. R. Welch, J. W. Fountain, T. G. Lugo, H. J. S. Huang and W. K. Cavenee (1998) In vitro loss of heterozygosity targets the PTEN/MMAC1 gene in melanoma. Proc. Natl Acad. Sci. USA 95, 94189423.
  • 82
    Hwang, P. H., H. K. Yi, D. S. Kim, S. Y. Nam, J. S. Kim and D. Y. Lee (2001) Suppression of tumorigenicity and metastasis in B16F10 cells by PTEN/MMAC1/TEP1 gene. Cancer Lett. 172, 8391.
  • 83
    Hennessy, B. T., D. L. Smith, P. T. Ram, Y. Lu and G. B. Mills (2005) Exploiting the PI3K/Akt pathway for cancer drug discovery. Nat. Rev. Drug Discov. 4, 9881004.
  • 84
    Harlan, J. E., H. S. Yoon, P. J. Hajduk and S. W. Fesik (1995) Structural characterization of the interaction between a pleckstrin homology domain and phosphatidylinositol 4,5-bisphosphate. Biochemistry 34, 98599864.
  • 85
    Nicholson, K. M. and N. G. Anderson (2002) The protein kinase B/Akt signalling pathway in human malignancy. Cell. Signal. 14, 381395.
  • 86
    Dhawan, P., A. B. Singh, D. L. Ellis and A. Richmond (2002) Constitutive activation of Akt/protein kinase B in melanoma leads to up-regulation of nuclear factor-kappaB and tumor progression. Cancer Res. 62, 73357342.
  • 87
    Dai, D. L., M. Martinka and G. Li (2005) Prognostic significance of activated Akt expression in melanoma: A clinicopathologic study of 292 cases. J. Clin. Oncol. 23, 14731482.
  • 88
    Slipicevic, A., R. Holm, M. T. Nguyen, P. J. Bøhler, B. Davidson and V. A. Flørenes (2005) Expression of activated Akt and PTEN in malignant melanomas: Relationship with clinical outcome. Am. J. Clin. Pathol. 124, 528536.
  • 89
    Kantrow, S. M., A. S. Boyd, D. L. Ellis, L. B. Nanney, A. Richmond, Y. Shyr and J. B. Robbins (2007) Expression of activated Akt in benign nevi, Spitz nevi and melanomas. J. Cutan. Pathol. 34, 593596.
  • 90
    Samuels, Y., Z. Wang, A. Bardelli, N. Silliman, J. Ptak, S. Szabo, H. Yan, A. Gazdar, S. M. Powell, G. J. Riggins, J. K. V. Willson, S. Markowitz, K. W. Kinzler, B. Vogelstein and V. E. Velculescu (2004) High frequency of mutations of the PIK3CA gene in human cancers. Science 304, 554.
  • 91
    Omholt, K., D. Kröckel, U. Ringborg and J. Hansson (2006) Mutations of PIK3CA are rare in cutaneous melanoma. Melanoma Res. 16, 197200.
  • 92
    Singh, R. S., A. H. Diwan, P. S. Zhang and V. G. Prieto (2007) Phosphoinositide 3-kinase is not overexpressed in melanocytic lesions. J. Cutan. Pathol. 34, 220225.
  • 93
    Curtin, J. A., M. S. Stark, D. Pinkel, N. K. Hayward and B. C. Bastian (2006) PI3-kinase subunits are infrequent somatic targets in melanoma. J. Invest. Dermatol. 126, 16601663.
  • 94
    Waldmann, V., J. Wacker and M. Deichmann (2002) Absence of mutations in the pleckstrin homology (PH) domain of protein kinase B (PKB/Akt) in malignant melanoma. Melanoma Res. 12, 4550.
  • 95
    Waldmann, V., J. Wacker and M. Deichmann (2001) Mutations of the activation-associated phosphorylation sites at codons 308 and 473 of protein kinase B are absent in human melanoma. Arch. Dermatol. Res. 293, 368372.
  • 96
    Stahl, J. M., A. Sharma, M. Cheung, M. Zimmerman, J. Q. Cheng, M. W. Bosenberg, M. Kester, L. Sandirasegarane and G. P. Robertson (2004) Deregulated Akt3 activity promotes development of malignant melanoma. Cancer Res. 64, 70027010.
  • 97
    Gomez-Gutierrez, J. G., V. Souza, H. Y. Hao, R. Montes de Oca-Lun, Y. B. Dong, H. S. Zhou and K. M. McMasters (2006) Adenovirus-mediated gene transfer of FKHRL1 triple mutant efficiently induces apoptosis in melanoma cells. Cancer Biol. Ther. 5, 875883.
  • 98
    Li, G., J. Kalabis, X. Xu, F. Meier, M. Oka, T. Bogenrieder and M. Herlyn (2003) Reciprocal regulation of MelCAM and Akt in human melanoma. Oncogene 22, 68916899.
  • 99
    Johnson, J. P. (1999) Cell adhesion molecules in the development and progression of malignant melanoma. Cancer Metastasis Rev. 18, 345357.
  • 100
    Kim, D., S. Kim, H. Koh, S.-O. Yoon, A.-S. Chung, K. S. Cho and J. Chung (2001) Akt/PKB promotes cancer cell invasion via increased motility and metalloproteinase production. FASEB J. 15, 19531962.
  • 101
    Park, B. K., X. Zeng and R. I. Glazer (2001) Akt1 induces extracellular matrix invasion and matrix metalloproteinase-2 activity in mouse mammary epithelial cells. Cancer Res. 61, 76477653.
  • 102
    Govindarajan, B., J. E. Sligh, B. J. Vincent, M. Li, J. A. Canter, B. J. Nickoloff, R. J. Rodenburg, J. A. Smeitink, L. Oberley, Y. Zhang, J. Slingerland, R. S. Arnold, J. D. Lambeth, C. Cohen, L. Hilenski, K. Griendling, M. Martinez-Diez, J. M. Cuezva and J. L. Arbiser (2007) Overexpression of Akt converts radial growth melanoma to vertical growth melanoma. J. Clin. Invest. 117, 719729.
  • 103
    Spofford, L. S., E. V. Abel, K. Boisvert-Adamo and A. E. Aplin (2006) Cyclin D3 expression in melanoma cells is regulated by adhesion-dependent phosphatidylinositol 3-kinase signaling and contributes to G1-S progression. J. Biol. Chem. 281, 2564425651.
  • 104
    Datta, S. R., H. Dudek, X. Tao, S. Masters, H. Fu, Y. Gotoh and M. E. Greenberg (1997) Akt phosphorylation of BAD couples survival signals to the cell-intrinsic death machinery. Cell 91, 231241.
  • 105
    Cardone, M. H., N. Roy, H. R. Stennicke, G. S. Salvesen, T. F. Franke, E. Stanbridge, S. Frisch and J. C. Reed (1998) Regulation of cell death protease caspase-9 by phosphorylation. Science 282, 13181321.
  • 106
    Brunet, A., A. Bonni, M. J. Zigmond, M. Z. Lin, P. Juo, L. S. Hu, M. J. Anderson, K. C. Arden, J. Blenis and M. E. Greenberg (1999) Akt promotes cell survival by phosphorylating and inhibiting a Forkhead transcription factor. Cell 96, 857868.
  • 107
    Romashkova, J. A. and S. S. Makarov (1999) NF-B is a target of Akt in anti-apoptotic PDGF signalling. Nature 401, 8690.
  • 108
    Veeman, M. T., J. D. Axelrod and R. T. Moon (2003) A second canon. Functions and mechanisms of β-catenin-independent Wnt signaling. Dev. Cell 5, 367377.
  • 109
    Liu, C., Y. Li, M. Semenov, C. Han, G. H. Baeg, Y. Tan, Z. Zhang, X. Lin and X. He (2002) Control of β-catenin phosphorylation/degradation by a dual-kinase mechanism. Cell 108, 837847.
  • 110
    Bejsovec, A. (2005) Wnt pathway activation: New relations and locations. Cell 120, 1114.
  • 111
    Cadigan, K. M. and Y. I. Liu (2006) Wnt signaling: Complexity at the surface. J. Cell Sci. 119, 395402.
  • 112
    Miller, J. R. (2002) The Wnts. Genome Biol. 3, REVIEWS3001.
  • 113
    Polakis, P. (2007) The many ways of Wnt in cancer. Curr. Opin. Genet. Dev. 7, 4551.
  • 114
    Rimm, D. L., K. Caca, G. Hu, F. B. Harrison and E. R. Fearon (1999) Frequent nuclear/cytoplasmic localization of β-catenin without exon 3 mutations in malignant melanoma. Am. J. Pathol. 154, 325329.
  • 115
    Rubinfeld, B., P. Robbins, M. El-Gamil, I. Albert, E. Porfiri and P. Polakis (1997) Stabilization of β-catenin by genetic defects in melanoma cell lines. Science 275, 17901792.
  • 116
    Worm, J., C. Christensen, K. Gronbaek, E. Tulchinsky and P. Guldberg (2004) Genetic and epigenetic alterations of the APC gene in malignant melanoma. Oncogene 23, 52155226.
  • 117
    Omholt, K., A. Platz, U. Ringborg and J. Hansson (2001) Cytoplasmic and nuclear accumulation of β-catenin is rarely caused by CTNNB1 exon 3 mutations in cutaneous malignant melanoma. Int. J. Cancer 92, 839842.
  • 118
    Reifenberger, J., C. B. Knobbe, M. Wolter, B. Blaschke, K. W. Schulte, T. Pietsch, T. Ruzicka and G. Reifenberger (2002) Molecular genetic analysis of malignant melanomas for aberrations of the WNT signaling pathway genes CTNNB1, APC, ICAT and BTRC. Int. J. Cancer 100, 549556.
  • 119
    Murakami, T., S. Toda, M. Fujimoto, M. Ohtsuki, H. R. Byers, T. Etoh and H. Nakagawa (2001) Constitutive activation of Wnt/β-catenin signaling pathway in migration-active melanoma cells: Role of LEF-1 in melanoma with increased metastatic potential. Biochem. Biophys. Res. Commun. 288, 815.
  • 120
    Kielhorn, E., E. Provost, D. Olsen, T. G. D’Aquila, B. L. Smith, R. L. Camp and D. L. Rimm (2003) Tissue microarray-based analysis shows phospho-β-catenin expression in malignant melanoma is associated with poor outcome. Int. J. Cancer 103, 652656.
  • 121
    Tago, K.-i., T. Nakamura, M. Nishita, J. Hyodo, S.-i. Nagai, Y. Murata, S. Adachi, S. Ohwada, Y. Morishita, H. Shibuya and T. Akiyama (2000) Inhibition of Wnt signaling by ICAT, a novel β-catenin-interacting protein. Genes Dev. 14, 17411749.
  • 122
    Goodall, J., S. Martinozzi, T. J. Dexter, D. Champeval, S. Carreira, L. Larue and C. R. Goding (2004) Brn-2 expression controls melanoma proliferation and is directly regulated by {β}-catenin. Mol. Cell. Biol. 24, 29152922.
  • 123
    Thomson, J. A., K. Murphy, E. Baker, G. R. Sutherland, P. G. Parsons and R. A. Sturm (1995) The brn-2 gene regulates the melanocytic phenotype and tumorigenic potential of human melanoma cells. Oncogene 11, 690700.
  • 124
    Dorsky, R. I., D. W. Raible and R. T. Moon (2000) Direct regulation of nacre, a zeB-Rafish MITF homolog required for pigment cell formation, by the Wnt pathway. Genes Dev. 14, 158162.
  • 125
    Takeda, K., K.-i. Yasumoto, R. Takada, S. Takada, K.-i. Watanabe, T. Udono, H. Saito, K. Takahashi and S. Shibahara (2000) Induction of melanocyte-specific microphthalmia-associated transcription factor by Wnt-3a. J. Biol. Chem. 275, 1401314016.
  • 126
    Hodgkinson, C. A., K. J. Moore, A. Nakayama, E. Steingrimsson, N. G. Copeland, N. A. Jenkins and H. Arnheiter (1993) Mutations at the mouse microphthalmia locus are associated with defects in a gene encoding a novel basic-helix-loop-helix-zipper protein. Cell 74, 395404.
  • 127
    Hughes, M. J., J. B. Lingrel, J. M. Krakowsky and K. P. Anderson (1993) A helix-loop-helix transcription factor-like gene is located at the mi locus. J. Biol. Chem. 268, 687690.
  • 128
    Widlund, H. R., M. A. Horstmann, E. R. Price, J. Cui, S. L. Lessnick, M. Wu, X. He and D. E. Fisher (2002) {β}-Catenin-induced melanoma growth requires the downstream target microphthalmia-associated transcription factor. J. Cell Biol. 158, 10791087.
  • 129
    Schepsky, A., K. Bruser, G. J. Gunnarsson, J. Goodall, J. H. Hallsson, C. R. Goding, E. Steingrimsson and A. Hecht (2006) The microphthalmia-associated transcription factor Mitf interacts with {β}-catenin to determine target gene expression. Mol. Cell. Biol. 26, 89148927.
  • 130
    Kawano, Y. and R. Kypta (2003) Secreted antagonists of the Wnt signalling pathway. J. Cell Sci. 116, 26272634.
  • 131
    Forget, M. A., S. Turcotte, D. Beauseigle, J. Godin-Ethier, S. Pelletier, J. Martin, S. Tanguay and R. Lapointe (2007) The Wnt pathway regulator DKK1 is preferentially expressed in hormone-resistant breast tumours and in some common cancer types. Br. J. Cancer 96, 646653.
  • 132
    Kuphal, S., S. Lodermeyer, F. Bataille, M. Schuierer, B. H. Hoang and A. K. Bosserhoff (2006) Expression of Dickkopf genes is strongly reduced in malignant melanoma. Oncogene 25, 50275036.
  • 133
    Mikheev, A. M., S. A. Mikheeva, R. Rostomily and H. Zarbl (2007) Dickkopf-1 activates cell death in MDA-MB435 melanoma cells. Biochem. Biophys. Res. Commun. 352, 675680.
  • 134
    Lin, Y. C., L. You, Z. Xu, B. He, C. T. Yang, J. K. Chen, I. Mikami, G. Clement, Y. Shi, K. Kuchenbecker, J. Okamoto, M. Kashani-Sabet and D. M. Jablons (2007) Wnt inhibitory factor-1 gene transfer inhibits melanoma cell growth. Hum. Gene Ther. 18, 379386.
  • 135
    You, L., B. He, Z. Xu, K. Uematsu, J. Mazieres, N. Fujii, I. Mikami, N. Reguart, J. K. McIntosh, M. Kashani-Sabet, F. McCormick and D. M. Jablons (2004) An anti-Wnt-2 monoclonal antibody induces apoptosis in malignant melanoma cells and inhibits tumor growth. Cancer Res. 64, 53855389.
  • 136
    Kikuchi, A., H. Yamamoto and S. Kishida (2007) Multiplicity of the interactions of Wnt proteins and their receptors. Cell. Signal. 19, 659671.
  • 137
    Iozzo, R. V., I. Eichstetter and K. G. Danielson (1995) Aberrant expression of the growth factor Wnt-5A in human malignancy. Cancer Res. 55, 34953499.
  • 138
    Crnogorac-Jurcevi, T., E. Efthimiou, P. Capelli, E. Blaveri, A. Baron, B. Terris, M. Jones, K. Tyson, C. Bassi, A. Scarpa and N. R. Lemoine (2001) Gene expression profiles of pancreatic cancer and stromal desmoplasia. Oncogene 20, 74377446.
  • 139
    Bittner, M., P. Meltzer, Y. Chen, Y. Jiang, E. Seftor, M. Hendrix, M. Radmacher, R. Simon, Z. Yakhini, A. Ben-Dor, N. Sampas, E. Dougherty, E. Wang, F. Marincola, C. Gooden, J. Lueders, A. Glatfelter, P. Pollock, J. Carpten, E. Gillanders, D. Leja, K. Dietrich, C. Beaudry, M. Berens, D. Alberts and V. Sondak (2000) Molecular classification of cutaneous malignant melanoma by gene expression profiling. Nature 406, 536540.
  • 140
    Carr, K. M., M. Bittner and J. T. Trent (2003) Gene-expression profiling in human cutaneous melanoma. Oncogene 22, 30763080.
  • 141
    Kuhl, M., L. C. Sheldahl, M. Park, J. R. Miller and R. T. Moon (2000) The Wnt/Ca2+ pathway: A new vertebrate Wnt signaling pathway takes shape. Trends Genet. 16, 279283.
  • 142
    Weeraratna, A. T., Y. Jiang, G. Hostetter, K. Rosenblatt, P. Duray, M. Bittner and J. M. Trent (2002) Wnt5a signaling directly affects cell motility and invasion of metastatic melanoma. Cancer Cell 1, 279288.
  • 143
    Weeraratna, A. T., D. Becker, K. M. Carr, P. H. Duray, K. P. Rosenblatt, S. Yang, Y. Chen, M. Bittner, R. L. Strausberg, G. J. Riggins, U. Wagner, O. P. Kallioniemi, J. M. Trent, P. J. Morin and P. S. Meltzer (2004) Generation and analysis of melanoma SAGE libraries: SAGE advice on the melanoma transcriptome. Oncogene 23, 22642274.
  • 144
    Dissanayake, S. K., M. Wade, C. E. Johnson, M. P. O’Connell, P. D. Leotlela, A. D. French, K. V. Shah, K. J. Hewitt, D. T. Rosenthal, F. E. Indig, Y. Jiang, B. J. Nickoloff, D. D. Taub, J. M. Trent, R. T. Moon, M. Bittner and A. T. Weeraratna (2007) The Wnt5A/protein kinase C pathway mediates motility in melanoma cells via the inhibition of metastasis suppressors and initiation of an epithelial to mesenchymal transition. J. Biol. Chem. 282, 1725917271.
  • 145
    Lahn, M. M. and K. L. Sundell (2004) The role of protein kinase C-alpha (PKC-alpha) in melanoma. Melanoma Res. 14, 8589.
  • 146
    Jonsson, M., K. Smith and A. L. Harris (1998) Regulation of Wnt5a expression in human mammary cells by protein kinase C activity and the cytoskeleton. Br. J. Cancer 78, 430438.
  • 147
    Weston, C. R. and R. J. Davis (2007) The JNK signal transduction pathway. Curr. Opin. Cell Biol. 19, 142149.
  • 148
    Karin, M. (1995) The regulation of AP-1 activity by mitogen-activated protein kinases. J. Biol. Chem. 270, 1648316486.
  • 149
    Davis, R. J. (2000) Signal transduction by the JNK group of MAP kinases. Cell 103, 239252.
  • 150
    Kennedy, N. J. and R. J. Davis (2003) Role of JNK in tumor development. Cell Cycle 2, 199201.
  • 151
    Nielsen, C., J. Thastrup, T. Bottzauw, M. Jaattela and T. Kallunki (2007) c-Jun NH2-terminal kinase 2 is required for Ras transformation independently of activator protein 1. Cancer Res. 67, 178185.
  • 152
    Yang, Y. M., F. Bost, W. Charbono, N. Dean, R. McKay, J. S. Rhim, C. Depatie and D. Mercola (2003) C-Jun NH(2)-terminal kinase mediates proliferation and tumor growth of human prostate carcinoma. Clin. Cancer Res. 9, 391401.
  • 153
    Cui, J., S. Y. Han, C. Wang, W. Su, L. Harshyne, M. Holgado-Madruga and A. J. Wong (2006) c-Jun NH(2)-terminal kinase 2alpha2 promotes the tumorigenicity of human glioblastoma cells. Cancer Res. 66, 1002410031.
  • 154
    Khatlani, T. S., M. Wislez, M. Sun, H. Srinivas, K. Iwanaga, L. Ma, A. E. Hanna, D. Liu, L. Girard, Y. H. Kim, J. R. Pollack, J. D. Minna Wistuba II and J. M. Kurie (2007) c-Jun N-terminal kinase is activated in non-small-cell lung cancer and promotes neoplastic transformation in human bronchial epithelial cells. Oncogene 26, 26582666.
  • 155
    Kennedy, N. J., H. K. Sluss, S. N. Jones, D. Bar-Sagi, R. A. Flavell and R. J. Davis (2003) Suppression of Ras-stimulated transformation by the JNK signal transduction pathway. Genes Dev. 17, 629637.
  • 156
    Uhlirova, M., H. Jasper and D. Bohmann (2005) Non-cell-autonomous induction of tissue overgrowth by JNK/Ras cooperation in a Drosophila tumor model. Proc. Natl Acad. Sci. USA 102, 1312313128.
  • 157
    Adler, V., A. Schaffer, J. Kim, L. Dolan and Z. Ronai (1995) UV irradiation and heat shock mediate JNK activation via alternate pathways. J. Biol. Chem. 270, 2607126077.
  • 158
    Chinenov, Y. and T. K. Kerppola (2001) Close encounters of many kinds: Fos–Jun interactions that mediate transcription regulatory specificity. Oncogene 20, 24382452.
  • 159
    Vogt, P. K. (2002) Fortuitous convergences: The beginnings of JUN. Nat. Rev. Cancer 2, 465469.
  • 160
    Angel, P., A. Szabowski and M. Schorpp-Kistner (2001) Function and regulation of AP-1 subunits in skin physiology and pathology. Oncogene 20, 24132423.
  • 161
    Bhoumik, A., T.-G. Huang, V. Ivanov, L. Gangi, R. F. Qiao, S. L. C. Woo, S.-H. Chen and Z.e. Ronai (2002) An ATF2-derived peptide sensitizes melanomas to apoptosis and inhibits their growth and metastasis. J. Clin. Invest. 110, 643650.
  • 162
    Mariani, O., C. Brennetot, J. M. Coindre, N. Gruel, C. Ganem, O. Delattre, M. H. Stern and A. Aurias (2007) JUN oncogene amplification and overexpression block adipocytic differentiation in highly aggressive sarcomas. Cancer Cell 11, 361374.
  • 163
    Vleugel, M. M., A. E. Greijer, R. Bos, E. Van Der Wall and P. J. Van Diest (2006) c-Jun activation is associated with proliferation and angiogenesis in invasive breast cancer. Hum. Pathol. 37, 668674.
  • 164
    Maeno, K., A. Masuda, K. Yanagisawa, H. Konishi, H. Osada, T. Saito, R. Ueda and T. Takahashi (2006) Altered regulation of c-Jun and its involvement in anchorage-independent growth of human lung cancers. Oncogene 25, 271277.
  • 165
    Behrens, A., W. Jochum, M. Sibilia and E. F. Wagner (2000) Oncogenic transformation by ras and fos is mediated by c-Jun N-terminal phosphorylation. Oncogene 19, 26572663.
  • 166
    Eferl, R., R. Ricci, L. Kenner, R. Zenz, J. P. David, M. Rath and E. F. Wagner (2003) Liver tumor development. c-Jun antagonizes the proapoptotic activity of p53. Cell 112, 181192.
  • 167
    Das, M., F. Jiang, H. K. Sluss, C. Zhang, K. M. Shokat, R. A. Flavell and R. J. Davis (2007) Suppression of p53-dependent senescence by the JNK signal transduction pathway. Proc. Natl Acad. Sci. USA 104, 1575915764.
  • 168
    Yamanishi, D. T., J. A. Buckmeier and F. L. Meyskens Jr (1991) Expression of c-Jun, JunB, and c-Fos protooncogenes in human primary melanocytes and metastatic melanomas. J. Invest. Dermatol. 97, 349353.
  • 169
    Rutberg, S. E., I. M. Goldstein, Y. M. Yang, C. W. Stackpole and Z. Ronai (1994) Expression and transcriptional activity of AP-1, CRE, and URE binding proteins in B16 mouse melanoma subclones. Mol. Carcinog. 10, 8287.
  • 170
    Jørgensen, K., B. Davidson and V. A. Flørenes (2006) Activation of c-Jun N-terminal kinase is associated with cell proliferation and shorter relapse-free period in superficial spreading malignant melanoma. Mod. Pathol. 19, 14461455.
  • 171
    Mingo-Sion, A. M., P. M. Marietta, E. Koller, D. M. Wolf and C. L. Van Den Berg (2004) Inhibition of JNK reduces G2/M transit independent of p53, leading to endoreduplication, decreased proliferation, and apoptosis in breast cancer cells. Oncogene 23, 596604.
  • 172
    Uzgare, A. R. and J. T. Isaacs (2004) Enhanced redundancy in Akt and mitogen-activated protein kinase-induced survival of malignant versus normal prostate epithelial cells. Cancer Res. 64, 61906199.
  • 173
    Gurzov, E. N., L. Bakiri, J. M. Alfaro, E. F. Wagner and M. Izquierdo (2007) Targeting c-Jun and JunB proteins as potential anticancer cell therapy. Oncogene. 2007 Jul 30 [Epub ahead of print].
  • 174
    Adjei, A. A. (2001) Blocking oncogenic Ras signaling for cancer therapy. J. Natl Cancer Inst. 93, 10621074.
  • 175
    Grafström, E., S. Egyházi, U. Ringborg, J. Hansson and A. Platz (2005) Biallelic deletions in INK4 in cutaneous melanoma are common and associated with decreased survival. Clin. Cancer Res. 11, 29912997.
  • 176
    Choi, B. Y., H. S. Choi, K. Ko, Y. Y. Cho, F. Zhu, B. S. Kang, S. P. Ermakova, W. Y. Ma, A. M. Bode and Z. Dong (2005) The tumor suppressor p16(INK4a) prevents cell transformation through inhibition of c-Jun phosphorylation and AP-1 activity. Nat. Struct. Mol. Biol. 12, 699707.
  • 177
    Ivanov, V. N., J. H. Kehrl and Z. Ronai (2000) Role of TRAF2/GCK in melanoma sensitivity to UV-induced apoptosis. Oncogene 19, 933942.
  • 178
    Arch, R. H., R. W. Gedrich and C. B. Thompson (2000) Translocation of TRAF proteins regulates apoptotic threshold of cells. Biochem. Biophys. Res. Commun. 272, 936945.
  • 179
    Rothe, M., M. G. Pan, W. J. Henzel, T. M. Ayres and D. V. Goeddel (1995) The TNFR2-TRAF signaling complex contains two novel proteins related to baculoviral inhibitor of apoptosis proteins. Cell 83, 12431252.
  • 180
    Natoli, G., A. Costanzo, A. Ianni, D. J. Templeton, J. R. Woodgett, C. Balsano and M. Levrero (1997) Activation of SAPK/JNK by TNF receptor 1 through a noncytotoxic TRAF2-dependent pathway. Science 275, 200203.
  • 181
    Liu, H., Y. C. Su, E. Becker, J. Treisman and E. Y. Skolnik (1999) A Drosophila TNF-receptor-associated factor (TRAF) binds the ste20 kinase Misshapen and activates Jun kinase. Curr. Biol. 9, 101104.
  • 182
    Ivanov, V. N., O. Fodstad and Z. Ronai (2001) Expression of ring finger-deleted TRAF2 sensitizes metastatic melanoma cells to apoptosis via up-regulation of p38, TNFalpha and suppression of NF-kappaB activities. Oncogene 20, 22432253.
  • 183
    Coppock, D. L., J. B. Tansey and L. Nathanson (1992) 12-O-tetradecanoylphorbol-13-acetate induces transient cell cycle arrest in G1 and G2 in metastatic melanoma cells: Inhibition of phosphorylation of p34cdc2. Cell Growth Differ. 3, 485494.
  • 184
    Mapelli, E., P. Banfi, E. Sala, M. Sensi, R. Supino, F. Zunino and R. A. Gambetta (1994) Effect of protein kinase C inhibitors on invasiveness of human melanoma clones expressing different levels of protein kinase C isoenzymes. Int. J. Cancer 57, 281286.
  • 185
    Arita, Y., K. R. O’Driscoll and I. B. Weinstein (1994) Growth inhibition of human melanoma-derived cells by 12-O-tetradecanoyl phorbol 13-acetate. Int. J. Cancer 56, 229235.
  • 186
    La Porta, C. A. and R. Comolli (1997) Activation of protein kinase C-alpha isoform in murine melanoma cells with high metastatic potential. Clin. Exp. Metastasis 15, 568579.
  • 187
    Dennis, J. U., N. M. Dean, C. F. Bennett, J. W. Griffith, C. M. Lang and D. R. Welch (1998) Human melanoma metastasis is inhibited following ex vivo treatment with an antisense oligonucleotide to protein kinase C-alpha. Cancer Lett. 128, 6570.
  • 188
    Oka, M. and U. Kikkawa (2005) Protein kinase C in melanoma. Cancer Metastasis Rev. 24, 287300.
  • 189
    Angel, P., M. Imagawa, R. Chiu, B. Stein, R. J. Imbra, H. J. Rahmsdorf, C. Jonat, P. Herrlich and M. Karin (1987) Phorbol ester-inducible genes contain a common cis element recognized by a TPA-modulated trans-acting factor. Cell 49, 729739.
  • 190
    Lopez-Bergami, P., H. Habelhah, A. Bhoumik, W. Zhang, L. H. Wang and Z. Ronai (2005) RACK1 mediates activation of JNK by protein kinase C [corrected]. Mol. Cell 19, 309320.
  • 191
    Gupta, S., D. Campbell, B. Derijard and R. J. Davis (1995) Transcription factor ATF2 regulation by the JNK signal transduction pathway. Science 267, 389393.
  • 192
    Van Dam, H. and M. Castellazzi (2001) Distinct roles of Jun: Fos and Jun: ATF dimers in oncogenesis. Oncogene 20, 24532464.
  • 193
    Tsai, E. Y., J. Jain, P. A. Pesavento, A. Rao and A. E. Goldfeld (1996) Tumor necrosis factor alpha gene regulation in activated T cells involves ATF-2/Jun and NFATp. Mol. Cell. Biol. 16, 459467.
  • 194
    Shimizu, M., Y. Nomura, H. Suzuki, E. Ichikawa, A. Takeuchi, M. Suzuki, T. Nakamura, T. Nakajima and K. Oda (1998) Activation of the rat cyclin A promoter by ATF2 and Jun family members and its suppression by ATF4. Exp. Cell Res. 239, 93103.
  • 195
    Huguier, S., J. Baguet, S. Perez, H. Van Dam and M. Castellazzi (1998) Transcription factor ATF2 cooperates with v-Jun to promote growth factor-independent proliferation in vitro and tumor formation in vivo. Mol. Cell. Biol. 18, 70207029.
  • 196
    Recio, J. A. and G. Merlino (2002) Hepatocyte growth factor/scatter factor activates proliferation in melanoma cells through p38 MAPK, ATF-2 and cyclin D1. Oncogene 21, 10001008.
  • 197
    Ronai, Z., Y. M. Yang, S. Y. Fuchs, V. Adler, M. Sardana and M. Herlyn (1998) ATF2 confers radiation resistance to human melanoma cells. Oncogene 16, 523531.
  • 198
    Ivanov, V. N., A. Bhoumik and Z. Ronai (2003) Death receptors and melanoma resistance to apoptosis. Oncogene 22, 31523161.
  • 199
    Berger, A. J., H. M. Kluger, N. Li, E. Kielhorn, R. Halaban, Z. Ronai and D. L. Rimm (2003) Subcellular localization of activating transcription factor 2 in melanoma specimens predicts patient survival. Cancer Res. 63, 81038107.
  • 200
    Bhoumik, A., S. Takahashi, W. Breitweiser, Y. Shiloh, N. Jones and Z. Ronai (2005) ATM-dependent phosphorylation of ATF2 is required for the DNA damage response. Mol. Cell 18, 577587.
  • 201
    Bhoumik, A., V. Ivanov and Z. Ronai (2001) Activating transcription factor 2-derived peptides alter resistance of human tumor cell lines to ultraviolet irradiation and chemical treatment. Clin. Cancer Res. 7, 331342.
  • 202
    Bhoumik, A., L. Gangi and Z. Ronai (2004) Inhibition of melanoma growth and metastasis by ATF2-derived peptides. Cancer Res. 64, 82228230.
  • 203
    Bhoumik, A., N. Jones and Z. Ronai (2004) Transcriptional switch by activating transcription factor 2-derived peptide sensitizes melanoma cells to apoptosis and inhibits their tumorigenicity. Proc. Natl Acad. Sci. USA 101, 42224227.
  • 204
    Abbas, S., A. Bhoumik, R. Dahl, S. Vasile, S. Krajewski, N. Cosford and Z. Ronai (2007) Preclinical studies of celastrol and acetyl isogambogic acid in melanoma. Clin. Cancer Res. 13, 67696778.
  • 205
    Bhoumik, A., C. DeRossi, W. Breitwieser, H. Kluger, S. Davis, A. Subtil, P. Meltzer, S. Krajewski, N. Jones and Z. Ronai. Suppressor role of activating transcription factor-2 (ATF2) in skin cancer. Proc. Natl Acad. Sci. USA (In press).
  • 206
    Verma, I. M., J. K. Stevenson, E. M. Schwarz, D. Van Antwerp and S. Miyamoto (1995) Rel/NF-kappa B/I kappa B family: Intimate tales of association and dissociation. Genes Dev. 9, 27232735.
  • 207
    Ueda, Y. and A. Richmond (2006) NF-κB activation in melanoma. Pigment Cell Res. 19, 112124.
  • 208
    Dixit, V. and T. W. Mak (2002) NF-kappaB signaling. Many roads lead to Madrid. Cell 111, 615619.
  • 209
    Ghosh, S. and M. Karin (2002) Missing pieces in the NF-kappaB puzzle. Cell 109 (Suppl.), S81S96.
  • 210
    Chen, X., K. Kandasamy and R. K. Srivastava (2003) Differential roles of RelA (p65) and c-Rel subunits of nuclear factor kappa B in tumor necrosis factor-related apoptosis-inducing ligand signaling. Cancer Res. 63, 10591066.
  • 211
    Karin, M., Y. Cao, R. Greten and Z. Li (2002) NF-κB in cancer: From innocent bystander to major culprit. Nat. Rev. Cancer 2, 301310.
  • 212
    Yang, J. and A. Richmond (2001) Constitutive IkappaB kinase activity correlates with nuclear factor-kappaB activation in human melanoma cells. Cancer Res. 61, 49014909.
  • 213
    Wang, D. and A. Richmond (2001) Nuclear factor-kappa B activation by the CXC chemokine melanoma growth-stimulatory activity/growth-regulated protein involves the MEKK1/p38 mitogen-activated protein kinase pathway. J. Biol. Chem. 276, 36503659.
  • 214
    Poser, I., D. Dominguez, A. G. De Herreros, A. Varnai, R. Buettner and A. K. Bosserhoff (2001) Loss of E-cadherin expression in melanoma cells involves up-regulation of the transcriptional repressor Snail. J. Biol. Chem. 276, 2466124666.
  • 215
    Kuphal, S., I. Poser, C. Jobin, C. Hellerbrand and A. K. Bosserhoff (2004) Loss of E-cadherin leads to upregulation of NFkappaB activity in malignant melanoma. Oncogene 23, 85098519.
  • 216
    Ivanov, V. and Z. Ronai (2000) p38 protects human melanoma cells from UV-induced apoptosis through down-regulation of NF-kappaB activity and Fas expression. Oncogene 19, 30033012.
  • 217
    Dhawan, P. and A. Richmond (2002) A novel NF-kappa B-inducing kinase-MAPK signaling pathway up-regulates NF-kappa B activity in melanoma cells. J. Biol. Chem. 277, 79207928.
  • 218
    Gray-Schopfer, V. C., M. Karasarides, R. Hayward and R. Marais (2007) Tumor necrosis factor-alpha blocks apoptosis in melanoma cells when B-Raf signaling is inhibited. Cancer Res. 67, 122129.
  • 219
    Fuchs, S. Y., A. Chen, Y. Xiong, Z. Q. Pan and Z. Ronai (1999) HOS, a human homolog of Slimb, forms an SCF complex with Skp1 and Cullin1 and targets the phosphorylation-dependent degradation of IkappaB and β-catenin. Oncogene 18, 20392046.
  • 220
    Soldatencov, V. A., A. Dritschilo, Z. Ronai and S. Y. Fuchs (1999) Inhibition of homologue of Slimb (HOS) function sensitizes human melanoma cells for apoptosis. Cancer Res. 59, 50855088.
  • 221
    Liu, J., K. G. Suresh Kumar, D. Yu, S. A. Molton, M. McMahon, M. Herlyn, A. Thomas-Tikhonenko and S. Y. Fuchs (2007) Oncogenic B-Raf regulates β-Trcp expression and NF-kappaB activity in human melanoma cells. Oncogene 26, 19541958.
  • 222
    Amiri, K. I. and A. Richmond (2005) Role of nuclear factor-kappa B in melanoma. Cancer Metastasis Rev. 24, 301313.
  • 223
    Madrid, L. V., M. W. Mayo, J. Y. Reuther and A. S. Baldwin Jr (2001) Akt stimulates the transactivation potential of the RelA/p65 Subunit of NF-kappa B through utilization of the Ikappa B kinase and activation of the mitogen-activated protein kinase p38. J. Biol. Chem. 276, 1893418940.
  • 224
    Koul, D., Y. Yao, J. L. Abbruzzese, W. K. Yung and S. A. Reddy (2001) Tumor suppressor MMAC/PTEN inhibits cytokine-induced NFkappaB activation without interfering with the IkappaB degradation pathway. J. Biol. Chem. 276, 1140211408.
  • 225
    Meyskens, F. L. Jr, J. A. Buckmeier, S. E. McNulty and N. B. Tohidian (1999) Activation of nuclear factor-kappa B in human metastatic melanoma cells and the effect of oxidative stress. Clin. Cancer Res. 5, 11971202.
  • 226
    Gao, K., D. L. Dai, M. Martinka and G. Li (2006) Prognostic significance of nuclear factor-kappa B p105/p50 in human melanoma and its role in cell migration. Cancer Res. 66, 83828388.
  • 227
    Philip, S. and G. C. Kundu (2003) Osteopontin induces nuclear factor kappa B-mediated promatrix metalloproteinase-2 activation through I kappa B alpha /IKK signaling pathways, and curcumin (diferulolylmethane) down-regulates these pathways. J. Biol. Chem. 278, 1448714497.
  • 228
    Boukerche, H., Z. Z. Su, L. Emdad, D. Sarkar and P. B. Fisher (2007) Mda-9/Syntenin regulates the metastatic phenotype in human melanoma cells by activating nuclear factor-kappaB. Cancer Res. 67, 18121822.
  • 229
    Rangaswami, H., A. Bulbule and G. C. Kundu (2006) Nuclear factor inducing kinase: A key regulator in osteopontin-induced MAPK/IkappaB kinase dependent NF-kappaB-mediated promatrix metalloproteinase-9 activation. Glycoconj. J. 23, 221232.
  • 230
    Rangaswami, H. and G. C. Kundu (2007) Osteopontin stimulates melanoma growth and lung metastasis through NIK/MEKK1-dependent MMP-9 activation pathways. Oncol. Rep. 18, 909915.
  • 231
    Ihle, J. N. and I. M. Kerr (1995) Jaks and STATs in signaling by the cytokine receptor superfamily. Trends Genet. 11, 6974.
  • 232
    Darnell, J. E., Jr (1997) STATs and gene regulation. Science 277, 16301635.
  • 233
    Rawlings, J. S., K. M. Rosler and D. A. Harrison (2004) The JAK/STAT signaling pathway. J. Cell Sci. 117, 12811283.
  • 234
    Ihle, J. N. (2001) The STAT family in cytokine signaling. Curr. Opin. Cell Biol. 13, 211217.
  • 235
    Mertens, C., M. Zhong, R. Krishnaraj, W. Zou, X. Chen and J. E. Darnell Jr (2006) Dephosphorylation of phosphotyrosine on STAT1 dimers requires extensive spatial reorientation of the monomers facilitated by the N-terminal domain. Genes Dev. 20, 33723381.
  • 236
    Heinrich, P. C., I. Behrmann, S. Haan, H. M. Hermanns, G. Muller-Newen and F. Schaper (2003) Principles of interleukin (IL)-6-type cytokine signalling and its regulation. Biochem. J. 374, 120.
  • 237
    Kubo, M., T. Hanada and A. Yoshimura (2003) Suppressors of cytokine signaling and immunity. Nat. Immunol. 4, 11691176.
  • 238
    Schindler, C., D. E. Levy and T. Decker (2007) JAK-STAT signaling: From interferons to cytokines. J. Biol. Chem. 282, 2005920063.
  • 239
    Ivanov, V. N., M. Krasilnikov and Z. Ronai (2002) Regulation of Fas expression by STAT3 and c-Jun is mediated by phosphatidylinositol 3-kinase-Akt signaling. J. Biol. Chem. 277, 49324944.
  • 240
    Bromberg, J. (2002) STAT proteins and oncogenesis. J. Clin. Invest. 109, 11391142.
  • 241
    Karamouzis, M. V., P. A. Konstantinopoulos and A. G. Papavassiliou (2007) The role of STATs in lung carcinogenesis: An emerging target for novel therapeutics. J. Mol. Med. 85, 427436.
  • 242
    Niu, G., R. Heller, R. Catlett-Falcone, D. Coppola, M. Jaroszeski, W. Dalton, R. Jove and H. Yu (1999) Gene therapy with dominant-negative STAT3 suppresses growth of the murine melanoma B16 tumor in vivo. Cancer Res. 59, 50595063.
  • 243
    Kortylewski, M., R. Jove and H. Yu (2005) Targeting STAT3 affects melanoma on multiple fronts. Cancer Metastasis Rev. 24, 315327.
  • 244
    Xie, T. X., D. Wei, M. Liu, A. C. Gao, F. Ali-Osman, R. Sawaya and S. Huang (2004) STAT3 activation regulates the expression of matrix metalloproteinase-2 and tumor invasion and metastasis. Oncogene 23, 35503560.
  • 245
    Xie, T. X., F. J. Huang, K. D. Aldape, S. H. Kang, M. Liu, J. E. Gershenwald, K. Xie, R. Sawaya and S. Huang (2006) Activation of STAT3 in human melanoma promotes brain metastasis. Cancer Res. 66, 31883196.
  • 246
    Yang, J., M. Chatterjee-Kishore, S. M. Staugaitis, H. Nguyen, K. Schlessinger, D. E. Levy and G. R. Stark (2005) Novel roles of unphosphorylated STAT3 in oncogenesis and transcriptional regulation. Cancer Res. 65, 939947.
  • 247
    Ivanov, V. N., A. Bhoumik, M. Krasilnikov, R. Raz, L. B. Owen-Schaub, D. Levy, C. M. Horvath and Z. Ronai (2001) Cooperation between STAT3 and c-Jun suppresses Fas transcription. Mol. Cell 7, 517528.
  • 248
    Niu, G., T. Bowman, M. Huang, S. Shivers, D. Reintgen, A. Daud, A. Chang, A. Kraker, R. Jove and H. Yu (2002) Roles of activated Src and STAT3 signaling in melanoma tumor cell growth. Oncogene 21, 70017010.
  • 249
    Mirmohammadsadegh, A., M. Hassan, W. Bardenheuer, A. Marini, A. Gustrau, S. Nambiar, A. Tannapfel, H. Bojar, T. Ruzicka and U. R. Hengge (2006) STAT5 phosphorylation in malignant melanoma is important for survival and is mediated through SRC and JAK1 kinases. J. Invest. Dermatol. 126, 22722280.
  • 250
    Tokita, T., C. Maesawa, T. Kimura, K. Kotani, K. Takahashi, T. Akasaka and T. Masuda (2007) Methylation STATus of the SOCS3 gene in human malignant melanomas. Int. J. Oncol. 30, 689694.
  • 251
    Fojtova, M., V. Boudny, A. Kovarik, L. Lauerova, L. Adamkova, K. Souckova, J. Jarkovsky and J. Kovarik (2007) Development of IFN-γ resistance is associated with attenuation of SOCS genes induction and constitutive expression of SOCS 3 in melanoma cells. Br. J. Cancer 97, 231237.
  • 252
    Wong, L. H., K. G. Krauer, I. Hatzinisiriou, M. J. Estcourt, P. Hersey, N. D. Tam, S. Edmondson, R. J. Devenish and S. J. Ralph (1997) Interferon-resistant human melanoma cells are deficient in ISGF3 components, STAT1, STAT2, and p48-ISGF3gamma. J. Biol. Chem. 272, 2877928785.
  • 253
    Kortylewski, M., W. Komyod, M. E. Kauffmann, A. Bosserhoff, P. C. Heinrich and I. Behrmann (2004) Interferon-gamma-mediated growth regulation of melanoma cells: Involvement of STAT1-dependent and STAT1-independent signals. J. Invest. Dermatol. 122, 414422.
  • 254
    Wang, W., H. D. Edington, U. N. Rao, D. M. Jukic, S. R. Land, S. Ferrone and J. M. Kirkwood (2007) Modulation of signal transducers and activators of transcription 1 and 3 signaling in melanoma by high-dose IFNalpha2b. Clin. Cancer Res. 13, 15231531.
  • 255
    Wellbrock, C., C. Weisser, J. C. Hassel, P. Fischer, J. Becker, C. S. Vetter, I. Behrmann, M. Kortylewski, P. C. Heinrich and M. Schartl (2005) STAT5 contributes to interferon resistance of melanoma cells. Curr. Biol. 15, 16291639.
  • 256
    Stewart, F. A., J. Denekamp and V. S. Randhawa (1982) Skin sensitization by misonidazole: A demonstration of uniform mild hypoxia. Br. J. Cancer 45, 869877.
  • 257
    Semenza, G. L. (1998) Hypoxia-inducible factor 1: Master regulator of O2 homeostasis. Curr. Opin. Genet. Dev. 8, 588594.
  • 258
    Harris, A. L. (2002) Hypoxia—A key regulatory factor in tumour growth. Nat. Rev. Cancer 2, 3847.
  • 259
    Distler, O., J. H. W. Distler, A. Scheid, T. Acker, A. Hirth, J. Rethage, B. A. Michel, R. E. Gay, U. Muller-Ladner, M. Matucci-Cerinic, K. H. Plate, M. Gassmann and S. Gay (2004) Uncontrolled expression of vascular endothelial growth factor and its receptors leads to insufficient skin angiogenesis in patients with systemic sclerosis. Circ. Res. 95, 109116.
  • 260
    Busca, R., E. Berra, C. Gaggioli, M. Khaled, K. Bille, B. Marchetti, R. Thyss, G. Fitsialos, L. Larribere, C. Bertolotto, T. Virolle, P. Barbry, J. Pouyssegur, G. Ponzio and R. Ballotti (2005) Hypoxia-inducible factor 1{alpha} is a new target of microphthalmia-associated transcription factor (MITF) in melanoma cells. J. Cell Biol. 170, 4959.
  • 261
    Kumar, S. M., H. Yu, R. Edwards, L. Chen, S. Kazianis, P. Brafford, G. Acs, M. Herlyn and X. Xu (2007) Mutant V600E B-Raf increases hypoxia inducible factor-1{alpha} expression in melanoma. Cancer Res. 67, 31773184.
  • 262
    Bedogni, B., S. M. Welford, D. S. Cassarino, B. J. Nickoloff, A. J. Giaccia and M. B. Powell (2005) The hypoxic microenvironment of the skin contributes to Akt-mediated melanocyte transformation. Cancer Cell 8, 443454.
  • 263
    Rofstad, E. K. and T. Danielsen (1998) Hypoxia-induced angiogenesis and vascular endothelial growth factor secretion in human melanoma. Br. J. Cancer 77, 897902.
  • 264
    Claffey, K. P., L. F. Brown, L. F. Del Aguila, K. Tognazzi, K.-T. Yeo, E. J. Manseau and H. F. Dvorak (1996) Expression of vascular permeability factor/vascular endothelial growth factor by melanoma cells increases tumor growth, angiogenesis, and experimental metastasis. Cancer Res. 56, 172181.
  • 265
    Lacal, P. M., F. Ruffini, E. Pagani and S. D’Atri (2005) An autocrine loop directed by the vascular endothelial growth factor promotes invasiveness of human melanoma cells. Int. J. Oncol. 27, 16251632.
  • 266
    Jones, D. T. and A. L. Harris (2006) Identification of novel small-molecule inhibitors of hypoxia-inducible factor-1 transactivation and DNA binding. Mol. Cancer Ther. 5, 21932202.
  • 267
    Nakayama, K., I. J. Frew, M. Hagensen, M. Skals, H. Habelhah, A. Bhoumik, T. Kadoya, H. Erdjument-Bromage, P. Tempst, P. B. Frappell, D. D. Bowtell and Z. Ronai (2004) Siah2 regulates stability of prolyl-hydroxylases, controls HIF1[alpha] abundance, and modulates physiological responses to hypoxia. Cell 117, 941952.
  • 268
    Piek, E. and A. B. Roberts (2001) Suppressor and oncogenic roles of transforming growth factor-β and its signaling pathways in tumorigenesis. Adv. Cancer Res. 83, 154.
  • 269
    Miyazono, K., P. Ten Dijke and C. H. Heldin (2000) TGF-β signaling by Smad proteins. Adv. Immunol. 75, 115157.
  • 270
    Berking, C., R. Takemoto, H. Schaider, L. Showe, K. Satyamoorthy, P. Robbins and M. Herlyn (2001) Transforming growth factor-{β}1 increases survival of human melanoma through stroma remodeling. Cancer Res. 61, 83068316.
  • 271
    Kang, S. H., Y. J. Bang, Y. H. Im, H. K. Yang, D. A. Lee, H. Y. Lee, H. S. Lee, N. K. Kim and S. J. Kim (1999) Transcriptional repression of the transforming growth factor-β type I receptor gene by DNA methylation results in the development of TGF-β resistance in human gastric cancer. Oncogene 18, 72807286.
  • 272
    Hussein, M. R. (2005) Transforming growth factor-β and malignant melanoma: Molecular mechanisms. J. Cutan. Pathol. 32, 389395.
  • 273
    Reed, J. A., Q. Lin, D. Chen, I. S. Mian and E. E. Medrano (2005) SKI pathways inducing progression of human melanoma. Cancer Metastasis Rev. 24, 265272.
  • 274
    Ehebauer, M., P. Hayward and A. Martinez-Arias (2006) Notch Signaling Pathway. Sci. STKE 2006, cm7.
  • 275
    Bolos, V., J. Grego-Bessa and J. L. De La Pompa (2007) Notch signaling in development and cancer. Endocr. Rev. 28, 339363.
  • 276
    Hoek, K., D. L. Rimm, K. R. Williams, H. Zhao, S. Ariyan, A. Lin, H. M. Kluger, A. J. Berger, E. Cheng, E. S. Trombetta, T. Wu, M. Niinobe, K. Yoshikawa, G. E. Hannigan and R. Halaban (2004) Expression profiling reveals novel pathways in the transformation of melanocytes to melanomas. Cancer Res. 64, 52705282.
  • 277
    Massi, D., F. Tarantini, A. Franchi, M. Paglierani, C. Di Serio, S. Pellerito, G. Leoncini, G. Cirino, P. Geppetti and M. Santucci (2006) Evidence for differential expression of Notch receptors and their ligands in melanocytic nevi and cutaneous malignant melanoma. Mod. Pathol. 19, 246254.
  • 278
    Qin, J.-Z., L. Stennett, P. Bacon, B. Bodner, M. J. C. Hendrix, R. E. B. Seftor, E. A. Seftor, N. V. Margaryan, P. M. Pollock, A. Curtis, J. M. Trent, F. Bennett, L. Miele and B. J. Nickoloff (2004) p53-independent NOXA induction overcomes apoptotic resistance of malignant melanomas. Mol. Cancer Ther. 3, 895902.
  • 279
    Balint, K., M. Xiao, C. C. Pinnix, A. Soma, I. Veres, I. Juhasz, E. J. Brown, A. J. Capobianco, M. Herlyn and Z.-J. Liu (2005) Activation of Notch1 signaling is required for {b}-catenin-mediated human primary melanoma progression. J. Clin. Invest. 115, 31663176.
  • 280
    Liu, Z.-J., M. Xiao, K. Balint, K. S. M. Smalley, P. B-Rafford, R. Qiu, C. C. Pinnix, X. Li and M. Herlyn (2006) Notch1 signaling promotes primary melanoma progression by activating mitogen-activated protein kinase/phosphatidylinositol 3-kinase-Akt pathways and up-regulating N-cadherin expression. Cancer Res. 66, 41824190.
  • 281
    Okuyama, R., H. Tagami and S. Aiba. Notch signaling: Its role in epidermal homeostasis and in the pathogenesis of skin diseases. J. Dermatol. Sci. (In press).
  • 282
    LoRusso, P. M., A. A. Adjei, M. Varterasian, S. Gadgeel, J. Reid, D. Y. Mitchell, L. Hanson, P. DeLuca, L. Bruzek, J. Piens, P. Asbury, K. Van Becelaere, R. Herrera, J. Sebolt-Leopold and M. B. Meyer (2005) Phase I and pharmacodynamic study of the oral MEK inhibitor CI-1040 in patients with advanced malignancies. J. Clin. Oncol. 23, 52815293.
  • 283
    Davies, B. R., A. Logie, J. S. McKay, P. Martin, S. Steele, R. Jenkins, M. Cockerill, S. Cartlidge and P. D. Smith (2007) AZD6244 (ARRY-142886), a potent inhibitor of mitogen-activated protein kinase/extracellular signal-regulated kinase kinase 1/2 kinases: Mechanism of action in vivo, pharmacokinetic/pharmacodynamic relationship, and potential for combination in preclinical models. Mol. Cancer Ther. 6, 22092219.
  • 284
    Richly, H., B. F. Henning, P. Kupsch, K. Passarge, M. Grubert, R. A. Hilger, O. Christensen, E. Brendel, B. Schwartz, M. Ludwig, C. Flashar, R. Voigtmann, M. E. Scheulen, S. Seeber and D. Strumberg (2006) Results of a Phase I trial of sorafenib (BAY 43-9006) in combination with doxorubicin in patients with refractory solid tumors. Ann. Oncol. 17, 866873.
  • 285
    Becker, J. C., J. M. Kirkwood, S. S. Agarwala, R. Dummer, D. Schrama and A. Hauschild (2006) Molecularly targeted therapy for melanoma. Cancer 107, 23172327.
  • 286
    Hersey, P. (2006) Apoptosis and melanoma: How new insights are effecting the development of new therapies for melanoma. Curr. Opin. Oncol. 18, 189196.