• 1
    Libbrecht L, Desmet V, Roskams T. Preneoplastic lesions in human hepatocarcinogenesis. Liver Int 2006; 25: 1627.
  • 2
    Guicciardi ME, Gores GJ. Apoptosis: a mechanism of acute and chronic liver injury. Gut 2005; 54: 102433.
  • 3
    Breitkopf K, Godoy P, Ciuclan L, et al. TGF-beta/Smad signalling in the injured liver. Z Gastroenterol 2006; 44: 5766.
  • 4
    Ganten TM, Koschny R, Haas TL, et al. Proteasome inhibition sensitizes hepatocellular carcinoma cells, but not human hepatocytes, to TRAIL. Hepatology 2005; 42: 58897.
  • 5
    Schafer ZT, Kornbluth S. The apoptosome: physiological, developmental, and pathological modes of regulation. Dev Cell 2006; 10: 54961.
  • 6
    Siegel PM, Massague J. Cytostatic and apoptotic actions of TGF-beta in homeostasis and cancer. Nat Rev Cancer 2003; 3: 80721.
  • 7
    Sanchez-Capelo A. Dual role of TGF-beta1 in apoptosis. Cytokine Growth Factor Rev 2005; 16: 1534.
  • 8
    Jang CW, Chen CH, Chen CC, et al. TGF-beta induces apoptosis through Smad-mediated expression of DAP kinase. Nat Cell Biol 2002; 4: 518.
  • 9
    Perlman R, Schiemann WP, Brooks MW, et al. TGF-beta-induced apoptosis is mediated by the adapter protein Daxx that facilitates JNK activation. Nat Cell Biol 2001; 3: 70814.
  • 10
    Takekawa M, Tatebayashi K, Itoh F, et al. Smad-dependent GADD45beta expression mediates delayed activation of p38 MAP kinase by TGF-beta. EMBO J 2002; 21: 647382.
  • 11
    Herrera B, Alvarez AM, Sanchez A, et al. Reactive oxygen species (ROS) mediates the mitochondrial-dependent apoptosis induced by transforming growth factor (beta) in fetal hepatocytes. FASEB J 2001; 15: 7415.
  • 12
    Ribeiro A, Bronk SF, Roberts PJ, et al. The transforming growth factor beta(1)-inducible transcription factor TIEG1, mediates apoptosis through oxidative stress. Hepatology 1999; 30: 14907.
  • 13
    Carmona-Cuenca I, Herrera B, Ventura JJ, et al. EGF blocks NADPH oxidase activation by TGF-beta in fetal rat hepatocytes, impairing oxidative stress, and cell death. J Cell Physiol 2006; 207: 32230.
  • 14
    Herrera B, Fernandez M, Benito M, Fabregat I. cIAP-1, but not XIAP, is cleaved by caspases during the apoptosis induced by TGF-beta in fetal rat hepatocytes. FEBS Lett 2002; 520: 936.
  • 15
    Valdes F, Murillo MM, Valverde AM, et al. Transforming growth factor-beta activates both pro-apoptotic and survival signals in fetal rat hepatocytes. Exp Cell Res 2004; 292: 20918.
  • 16
    Breuhahn K, Longerich T, Schirmacher P. Dysregulation of growth factor signalling in human hepatocellular carcinoma. Oncogene 2006; 25: 3787800.
  • 17
    Mead JE, Fausto N. Transforming growth factor alpha may be a physiological regulator of liver regeneration by means of an autocrine mechanism. Proc Natl Acad Sci USA 1989; 86: 1558862.
  • 18
    Jo M, Stolz DB, Esplen JE, et al. Cross-talk between epidermal growth factor receptor and c-Met signal pathways in transformed cells. J Biol Chem 2000; 275: 880611.
  • 19
    Sebolt-Leopold JS, English JM. Mechanisms of drug inhibition of signalling molecules. Nature 2006; 441: 45762.
  • 20
    Schulze-Bergkamen H, Brenner D, Krueger A, et al. Hepatocyte growth factor induces Mcl-1 in primary human hepatocytes and inhibits CD95-mediated apoptosis via Akt. Hepatology 2004; 39: 6454.
  • 21
    Wajant H, Pfizenmaier K, Scheurich P. Tumor necrosis factor signaling. Cell Death Differ 2003; 10: 4565.
  • 22
    Gonzalez FJ. Role of β-catenin in the adult liver. Hepatology 2006; 43: 6503.
  • 23
    Bruix J, Hessheimer AJ, Forner A, et al. New aspects of diagnosis and therapy of hepatocellular carcinoma. Oncogene 2006; 25: 384856.
  • 24
    Bao JJ, Zhang WW, Kuo MT. Adenoviral delivery of recombinant DNA into transgenic mice bearing hepatocellular carcinomas. Hum Gene Ther 1996; 7: 35565.
  • 25
    Farazi PA, Glickman J, Hormer J, Depinho RA. Cooperative interactions of p53 mutation, telomere dysfunction, and chronic liver damage in hepatocellular carcinoma progression. Cancer Res 2006; 66: 476673.
  • 26
    Thorgeirsson S S, Teramoto T, Factor V M. Dysregulation of apoptosis in hepatocellular carcinoma. Semin Liver Dis 1998; 18: 11522.
  • 27
    Yang Y-A, Zhang G-M, Feigenbaum L, Zhang YE. Smad3 reduces susceptibility to hepatocarcinoma by sensitizing hepatocytes to apoptosis through downregulation of Bcl-2. Cancer Cell 2006; 9: 44557.
  • 28
    Rossmanith W, Schulte-Hermann R. Biology of transforming growth factor beta in hepatocarcinogenesis. Microsc Res Technol 2001; 52: 4306.
  • 29
    Fabregat I, Herrera B, Fernandez M, et al. Epidermal growth factor impairs the cytochrome c/caspase-3 apoptotic pathway induced by transforming growth factor beta in rat fetal hepatocytes via a phosphoinositide 3-kinase-dependent pathway. Hepatology 2000; 32: 52835.
  • 30
    Breuhahn K, Longerich T, Schirmacher P. Dysregulation of growth factor signaling in human hepatocellular carcinoma. Oncogene 2006; 25: 3787800.
  • 31
    Murillo MM, Del Castillo G, Sanchez A, et al. Involvement of EGF receptor and c-Src in the survival signals induced by TGF-beta1 in hepatocytes. Oncogene 2005; 24: 45807.
  • 32
    Borrell-Pages M, Rojo F, Albanell J, et al. TACE is required for the activation of the EGFR by TGF-alpha in tumors. EMBO J 2003; 22: 11142.
  • 33
    Ding X, Yang LY, Huang GW, et al. ADAM17 mRNA expression and pathological features of hepatocellular carcinoma. World J Gastroenterol 2004; 10: 27359.
  • 34
    Horie Y, Suzuki A, Kataoka E, et al. Hepatocyte-specific Pten deficiency results in steatohepatitis and hepatocellular carcinomas. J Clin Invest 2004; 113: 177483.
  • 35
    Zender L, Spector MS, Xue W, et al. Identification and validation of oncogenes in liver cancer using an integrative oncogenomic approach. Cell 2006; 125: 125367.
  • 36
    Arsura M, Cavin LG. Nuclear factor-κB and liver carcinogenesis. Cancer Lett 2005; 229: 15769.
  • 37
    Cavin LG, Wang F, Factor VM, et al. Transforming growth factor-alpha inhibits the intrinsic pathway of c-Myc-induced apoptosis through activation of nuclear factor-kappab in murine hepatocellular carcinomas. Mol Cancer Res 2005; 3: 40312.
  • 38
    Takehara T, Liu X, Fujimoto J, et al. Expression and role of Bcl-xl in human hepatocellular carcinomas. Hepatology 2001; 34: 5561.
  • 39
    Notarbartolo M, Cervello M, Giannitrapani L, et al. Expression of IAPs and alternative splice variants in hepatocellular carcinoma tissues and cells. Ann NY Acad Sci 2004; 1028: 28993.
  • 40
    Kaur S, Wang F, Venkatraman M, Arsura M. X-linked inhibitor of apoptosis (XIAP) inhibits c-Jun N-terminal kinase 1 (JNK1) activation by transforming growth factor beta 1 (TGF-beta1) through ubiquitin-mediated proteosomal degradation of the TGF-beta1-activated kinase 1 (TAK1). J Biol Chem 2005; 280: 38599608.
  • 41
    Qiao L, Zhang H, Yu J, et al. Constitutive activation of NF-kappab in human hepatocellular carcinoma: evidence of a cytoprotective role. Human Gene Ther 2006; 17: 809.
  • 42
    Lian Z, Liu J, Pan J, et al. A cellular gene up-regulated by hepatitis B virus-encoded X antigen promotes hepatocellular growth and survival. Hepatology 2001; 34: 14657.
  • 43
    Suzuki A, Hayashida M, Kawano H, et al. Hepatocyte growth factor promotes cell survival from fas-mediated cell death in hepatocellular carcinoma cells via Akt activation and Fas-death-inducing signaling complex suppression. Hepatology 2000; 32: 796802.
  • 44
    Calvisi DF, Ladu S, Gorden A, et al. Ubiquitous activation of Ras and Jak/Stat pathways in human HCC. Gastroenterology 2006; 130: 111728.
  • 45
    Yoshida T, Hisamoto T, Akiba J, et al. Spreds, inhibitors of the Ras/ERK signal transduction, are dysregulated in human hepatocellular carcinoma and linked to the malignant phenotype of tumors. Oncogene 2006; advance online publication; doi: DOI: 10.1038/sj.onc.1209635.
  • 46
    Kim YC, Song KS, Yoon G, et al. Activated ras oncogene collaborates with hbx gene of hepatitis B virus to transform cells by suppressing HBx-mediated apoptosis. Oncogene 2001; 20: 1623.
  • 47
    Sieghart W, Losert D, Strommer S, et al. Mcl-1 overexpression in hepatocellular carcinoma: a potential target for antisense therapy. J Hepatol 2006; 44: 1517.
  • 48
    Beerheide W, Tan YJ, Teng E, et al. Down-regulation of proapoptotic proteins Bax and Bcl-X(S) in p53 overexpression hepatocellular carcinomas. Biochem Biophys Res Commun 2000; 273: 5461.
  • 49
    Chen GG, Lai PB, Chan PK, et al. Decreased expression of Bid in human hepatocellular carcinoma is related to hepatitis B virus X protein. Eur J Cancer 2001; 37: 1695702.
  • 50
    Disson O, Haouzi D, Desagher S, et al. Impaired clearance of virus-infected hepatocytes in transgenic mice expressing the hepatitis C virus polyprotein. Gastroenterology 2004; 126: 85972.
  • 51
    Gotzmann J, Mikula M, Eger A, et al. Molecular aspects of epithelial cell plasticity: implications for local tumor invasion and metastasis. Mutat Res 2004; 566: 920.
  • 52
    Valdes F, Alvarez AM, Locascio A, et al. The epithelial mesenchymal transition confers resistance to the apoptotic effects of transforming growth factor beta in fetal rat hepatocytes. Mol Cancer Res 2002; 1: 6878.
  • 53
    Vega S, Morales AV, Ocana OH, et al. Snail blocks the cell cycle and confers resistance to cell death. Genes Dev 2004; 18: 113143.
  • 54
    Lee HC, Kim M, Wands JR. Wnt/frizzled signaling in hepatocellular carcinoma. Front Biosci 2006; 11: 190115.
  • 55
    Lian Z, Liu J, Li X, et al. Enhanced cell survival of Hep3B cells by the hepatitis Bx antigen effector, URG11, is associated with upregulation of beta-catenin. Hepatology 2006; 43: 41524.