• 1
    Shaib Y, El-Serag HB. The epidemiology of cholangiocarcinoma. Semin Liver Dis 2004; 24: 11525.
  • 2
    De Groen PC, Gores GJ, LaRusso NF, Gunderson LL, Nagorney DM. Biliary tract cancers. N Engl J Med 1999; 341: 136878.
  • 3
    Ito Y. Molecular basis of tissue-specific gene expression mediated by the runt domain transcription factor PEBP2/CBF. Genes Cells 1999; 4: 68596.
  • 4
    Levanon D, Bernstein Y, Negreanu V et al. A large variety of alternatively spliced and differentially expressed mRNAs are encoded by the human acute myeloid leukemia gene AML1. DNA Cell Biol 1996; 15: 17585.
  • 5
    Li QL, Ito K, Sakakura C et al. Causal relationship between the loss of RUNX3 expression and gastric cancer. Cell 2002; 109: 11324.
  • 6
    Li QL, Kim HR, Kim WJ et al. Transcriptional silencing of the RUNX3 gene by CpG hypermethylation is associated with lung cancer. Biochem Biophys Res Commun 2004; 314: 2238.
  • 7
    Yanagawa N, Tamura G, Oizumi H, Takahashi N, Shimazaki Y, Motoyama T. Promoter hypermethylation of tumor suppressor and tumor-related genes in non-small cell lung cancers. Cancer Sci 2003; 94: 58992.
  • 8
    Xiao WH, Liu WW. Hemizygous deletion and hypermethylation of RUNX3 gene in hepatocellular carcinoma. World J Gastroenterol 2004; 10: 37680.
  • 9
    Kim TY, Lee HJ, Hwang KS et al. Methylation of RUNX3 in various types of human cancers and premalignant stages of gastric carcinoma. Lab Invest 2004; 84: 47984.
  • 10
    Goel A, Arnold CN, Tassone P et al. Epigenetic inactivation of RUNX3 in microsatellite unstable sporadic colon cancers. Int J Cancer 2004; 112: 7549.
  • 11
    Wada M, Yazumi S, Takaishi S et al. Frequent loss of RUNX3 gene expression in human bile duct and pancreatic cancer cell lines. Oncogene 2004; 23: 24017.
  • 12
    Kang GH, Lee S, Lee HJ, Hwang KS. Aberrant CpG island hypermethylation of multiple genes in prostate cancer and prostatic intraepithelial neoplasia. J Pathol 2004; 202: 23340.
  • 13
    Hanai J, Chen LF, Kanno T et al. Interaction and functional cooperation of PEBP2/CBF with Smads. Synergistic induction of the immunoglobulin germline Cα promoter. J Biol Chem 1999; 274: 31 57782.
  • 14
    Heldin CH, Miyazono K, Ten Dijke P. TGF-β signalling from cell membrane to nucleus through SMAD proteins. Nature 1997; 390: 46571.
  • 15
    Massague J. How cells read TGF-β signals. Nat Rev Mol Cell Biol 2000; 1: 16978.
  • 16
    Li JM, Nichols MA, Chandrasekharan S, Xiong Y, Wang XF. Transforming growth factor beta activates the promoter of cyclin-dependent kinase inhibitor p15INK4B through an Sp1 consensus site. J Biol Chem 1995; 270: 26 7503.
  • 17
    Sandhu C, Garbe J, Bhattacharya N et al. Transforming growth factor beta stabilizes p15INK4B protein, increases p15INK4B–cdk4 complexes, and inhibits cyclin D1–cdk4 association in human mammary epithelial cells. Mol Cell Biol 1997; 17: 245867.
  • 18
    Ducos K, Panterne B, Fortunel N, Hatzfeld A, Monier MN, Hatzfeld J. p21 (cip1) mRNA is controlled by endogenous transforming growth factor-β1 in quiescent human hematopoietic stem/progenitor cells. J Cell Physiol 2000; 184: 805.
  • 19
    Miyazaki M, Ohashi R, Tsuji T, Mihara K, Gohda E, Namba M. Transforming growth factor-β1 stimulates or inhibits cell growth via down- or up-regulation of p21/Waf1. Biochem Biophys Res Commun 1998; 246: 87380.
  • 20
    Florenes VA, Bhattacharya N, Bani MR, Ben-David Y, Kerbel RS, Slingerland JM. TGF-β mediated G1 arrest in a human melanoma cell line lacking p15INK4B: evidence for cooperation between p21Cip1/WAF1 and p27Kip1. Oncogene 1996; 13: 244757.
  • 21
    Tadlock L, Yamagiwa Y, Hawker J, Marienfeld C, Patel T. Transforming growth factor-beta inhibition of proteasomal activity: a potential mechanism of growth arrest. Am J Physiol Cell Physiol 2003; 285: C27785.
  • 22
    Vivanco I, Sawyers CL. The phosphatidylinositol 3-kinase AKT pathway in human cancer. Nat Rev Cancer 2002; 2: 489501.
  • 23
    Seoane J, Le HV, Shen L, Anderson SA, Massague J. Integration of Smad and forkhead pathways in the control of neuroepithelial and glioblastoma cell proliferation. Cell 2004; 117: 21123.
  • 24
    Conery AR, Cao Y, Thompson EA, Townsend CM Jr, Ko TC, Luo K. Akt interacts directly with Smad3 to regulate the sensitivity to TGF-β induced apoptosis. Nat Cell Biol 2004; 6: 36672.
  • 25
    Massague J, Seoane J, Wotton D. Smad transcription factors. Genes Dev 2005; 19: 2783810.
  • 26
    Ito K, Liu Q, Salto-Tellez M et al. RUNX3, a novel tumor suppressor, is frequently inactivated in gastric cancer by protein mislocalization. Cancer Res 2005; 65: 774350.
  • 27
    Iwai A, Marusawa H, Kiuchi T et al. Role of a novel oncogenic protein, gankyrin, in hepatocyte proliferation. J Gastroenterol 2003; 38: 7518.
  • 28
    Yazumi S, Ko K, Watanabe N et al. Disrupted transforming growth factor-β signaling and deregulated growth in human biliary tract cancer cells. Int J Cancer 2000; 86: 7829.
  • 29
    Sakakura C, Hasegawa K, Miyagawa K et al. Possible involvement of RUNX3 silencing in the peritoneal metastases of gastric cancers. Clin Cancer Res 2005; 11: 647988.
  • 30
    Torquati A, O’Rear L, Longobardi L, Spagnoli A, Richards WO, Daniel BR. RUNX3 inhibits cell proliferation and induces apoptosis by reinstating transforming growth factor beta responsiveness in esophageal adenocarcinoma cells. Surgery 2004; 136: 31016.
  • 31
    Fukamachi H, Ito K. Growth regulation of gastric epithelial cells by Runx3. Oncogene 2004; 23: 43305.
  • 32
    Wei D, Gong W, Oh SC et al. Loss of RUNX3 expression significantly affects the clinical outcome of gastric cancer patients and its restoration causes drastic suppression of tumor growth and metastasis. Cancer Res 2005; 65: 480916.
  • 33
    Ohgushi M, Kuroki S, Fukamachi H et al. Transforming growth factor beta-dependent sequential activation of Smad, Bim, and caspase-9 mediates physiological apoptosis in gastric epithelial cells. Mol Cell Biol 2005; 25: 10 01728.
  • 34
    Yamamura Y, Lee WL, Inoue KI et al. RUNX3 cooperates with FoxO3a to induce apoptosis in gastric cancer cells. J Biol Chem 2006; 281: 526776.
  • 35
    Chi XZ, Yang JO, Lee KY et al. RUNX3 suppresses gastric epithelial cell growth by inducing p21 (WAF1/Cip1) expression in cooperation with transforming growth factor β-activated SMAD. Mol Cell Biol 2005; 25: 8097107.
  • 36
    Donovan JC, Rothenstein JM, Slingerland JM. Non-malignant and tumor-derived cells differ in their requirement for p27Kip1 in transforming growth factor-β-mediated G1 arrest. J Biol Chem 2002; 277: 41 68692.
  • 37
    Baldwin RL, Tran H, Karlan BY. Loss of c-myc repression coincides with ovarian cancer resistance to transforming growth factor beta growth arrest independent of transforming growth factor beta/Smad signaling. Cancer Res 2003; 63: 141319.
  • 38
    Yagi K, Furuhashi M, Aoki H et al. c-myc is a downstream target of the Smad pathway. J Biol Chem 2002; 277: 85461.
  • 39
    Osaki M, Moriyama M, Adachi K et al. Expression of RUNX3 protein in human gastric mucosa, intestinal metaplasia and carcinoma. Eur J Clin Invest 2004; 34: 60512.