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1994 Fiscal Year Final Research Report Summary

Analysis of genetic changes in growth factor related genes and tumor suppressor genes implicated in the development, proliferation and invasion of human stomach cancer.

Research Project

Project/Area Number 04404030
Research Category

Grant-in-Aid for General Scientific Research (A)

Allocation TypeSingle-year Grants
Research Field Human pathology
Research InstitutionHIROSHIMA UNIVERSITY

Principal Investigator

TAHARA Eiichi  Hiroshima University School of Medicine, Department of Pathology, Professor, 医学部, 教授 (00033986)

Co-Investigator(Kenkyū-buntansha) KUNIAYSU Hiroki  Hiroshima University School of Medicine, Department of Pathology, Assistant, 医学部, 助手 (00253055)
YOKOZAKI Hiroshi  Hiroshima University School of Medicine, Department of Pathology, Assistant Prof, 医学部, 講師 (10200891)
YASUI Wataru  Hiroshima University School of Medicine, Department of Pathology, Associate Prof, 医学部, 助教授 (40191118)
Project Period (FY) 1992 – 1994
KeywordsGastric cancer / APC gene / Intestinal metaplasia / Genetic instability / HGF / C-met
Research Abstract

Gene changes in multiple oncogenes, multiple suppressor genes and genetic instability may be implicated in stomach carcinogenesis. Among them, aberrant expression and amplification of the c-met gene, inactivation of the p53 gene and CD44 abnormal transcripts are common events of both well differentiated type and poorly differentiated type gastric cancers. Amplification of the cyclin E gene is also observed in gastric cancer regardless of histological types. Decreased expression and mutations of the pic1 (p21) gene occurs independent of the p53 mutations. In addition, K-ras mutations, c-erbB-2 gene amplification, loss of heterozygosity (LOH) and mutations of the APC gene, LOH of the bcl-2 gene, and LOH at DCC locus are preferentially associated with well differentiated type gastric cancer. Precancerous lesions including hyperplastic polyp, intestinal metaplasia and adenoma also show genetic changes which are found in well differentiated type cancer. Conversely, genetic instability may be involved in the first step of stomach carcinogenesis for poorly differentiated type. Reduction or loss of cadherin and catenins, K-sam gene amplification, and c-met gene amplification are necessary for the development and progression of poorly differentiated type or scirrhous carcinoma.
Interaction between cell-adhesion molecules in the c-met expressed tumor cells and hepatocyte growth factor from stromal cells is involved in the morphogenesis of two types of gastric cancer. Taken together, different genetic pathways of stomach carcinogenesis may exist for well differentiated and poorly differentiated gastric cancers. Some of the former may develop by a cumulative series of gene alterations similar to those of colorectal cancer.

  • Research Products

    (70 results)

All Other

All Publications (70 results)

  • [Publications] Ito.M: "Growth inhibition of transforming growth factorβ on human gastric carcinoma cells:Receptor and postreceptor signaling." Cancer Res.52. 295-300 (1992)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ito.M: "Reduced levels of transforming growth factor-beta type Ireceptor in human gastric carcinomas." Jpn.J.Cancer Res.83. 86-92 (1992)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kameda,T.: "Tyrosine kinase activity of epidermal growth factor receptor in human gastric carcinomas." Path.Res.Pract.188. 37-43 (1992)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Mattar,R.: "p53 gene mutations in gastric cancer cell lines." Oncol.(Life Sci.Adv.). 11. 7-12 (1992)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yokozaki,H.: "p53 point mutations in primary human gastric carcinomas." J.Cancer Res.Clin.Oncol.119. 67-70 (1992)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kuniyasu,H.: "Frequent amplification of the c-met gene in scirrhous type stomach cancer." Biochem.Biophys.Res.Commun.189. 227-232 (1992)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kitadai,Y.: "The level of a transcription factor Spl is correlated with the expression of EGF receptor in human gastric carcinomas." Biochem.Biophys.Res.Commun.189. 1342-1348 (1992)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nakatsuru,S.: "Somatic mutation of the APC gene in gastric cancer:Frequent mutations in very well differentiated adenocarcinoma and signet ring cell carcinoma." Human Molecular Genetics. 1. 559-563 (1992)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Shimamoto,T: "Flow cytometric DNA anlysis of gastric smooth mucsle tumors." Cancer. 70. 2031-2034 (1992)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yasui,W.: "Increased expression of p34^<cdc2> and its kinase activity in human gastric and colonic carcinomas." Int.J.Cancer. 53. 36-41 (1993)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nakayama,H.: "Reduced expression of nm23 is associated with metastasis of human gastric carcinomas." Jpn.J.Cancer.Res.84. 184-190 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tahara,E.: "Molecular mechanism of stomach carcinogenesis." J.Cancer.Res.Clin.Oncol.119. 265-272 (1993)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tohdo,H: "p53 gene mutations in gastric adenomas" Virchows Archiv B(Cell Pathol.). 63. 191-195 (1993)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yasui,W.: "Expression of P-cadherin in gastric carcinomas and its reduction in tumor progression." Int.J.Cancer. 54. 49-52 (1993)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kitadai,Y.: "GC factor represses transcription of several growth factor/receptor genes and causes growth inhibition of human gastric carcinoma cell lines." Cell Growth & Differentiation. 4. 291-296 (1993)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yokozaki,H.: "Biologic effect of human hepatocoyte growth factor on human gastric carcinoma cell lines." Int.J.Oncology. 3. 89-93 (1993)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kyo,E.: "Reduced tumorigenicity and cell motility of a gastric carcinoma cell lineby introduction of wild-type p53 gene." Int.J.Oncol.3. 265-271 (1993)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kiatadai,Y.: "Expression of amphiregulin,a novel gene of the epidermal growth factor family in human gastric carcinomas." Jpn.J.Cancer.Res.84. 879-884 (1993)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kuniyasu,H.: "Aberrant expression of c-met mRNA in human gastric carcinomas." Int.J.Cancer. 55. 72-75 (1993)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ito,R.: "Interleukin 1α acts as an autocrine growth stimulator for human gastric carcinoma cells." Cancer Res.53. 4102-4106 (1993)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tahara,E.: "Gene alterations in intestinal metaplasia and gastric cancer." European J.Gastroenterology & Hepatology. 6. S97-S101 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tannapfel,A.: "Effect of hepatocyte growth factor on the expression of E-and P-cadherin in gastric carcinoma cell lines." Virchows Archiv. 425. 139-144 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kuniyasu,H.: "Frequent loss of heterozygosity of the long arm of chromosome 7 is closely associated with progression of human gastric carcinomas" Int.J.Cancer. 59. 597-600 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kuniyasu,H.: "Expression of cripto in human gastric carcinomas:an association with tumor stage and prognosis." J.Exp.Clin.Cancer Res.13. 151-157 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Lotan,R.: "Expression of a 31-kDa lactoside-binding lectin in normal human gastric mucosa and in primary and metastatic gastric carcinomas." Int.J.Cancer. 56. 474-480 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ayhan,A.: "Loss of heterozygosity at the bcl-2 gene locus and expression of bcl-2 in human gastric and colorectal carcinomas." Jpn.J.Cancer Res.85. 584-591 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kozako,Y.: "Expression of β1 integrin in human gastric carcinomas:correlation with histological type and tumor progression." Int.J.Oncology. 5. 225-230 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Saeki,T.: "Immunohistochemical detection of cripto-1,amphiregulin and transforming growth factor alpha in human gastric carcinomas and intestinal metaplasias." Int.J.Oncology. 5. 215-223 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yokozaki,H.: "Expression of CD44 abnormal transcripts in human gastric carcinomas." Cancer Letters. 83. 229-234 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Horii,A.: "Frequent replication errors at microsatellite loci in tumors of patients with multiple primary cancers." Cancer Res.54. 3373-3375 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Sugimura,T.: "Meeting Report,First International Workshop of the Princess Takamatsu Cancer Research Fund:Intestinal Metaplasia and Gastric Cancer." Molecular Carcinogenesis. 11. 1-7 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ito,H.: "Gastric Cancer" Springer-Verlag,Tokyo, 446 (1993)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tahara,E.: "Gastric Cancer" Springer-Verlag,Tokyo, 446 (1993)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tahara,E.: "Gann Monograph on Cancer Research" Japan Scientific Societies Press, 178 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tahara,E.: "Proceedings of the 24th International Symposium of the Princess Takamatsu Cancer Research Fund" Princeton Scientific Publishing Co.,Inc.,Princeton,New Jersey,USA, 357 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tannapfel A,Yasui W,Yokozaki H,Wittekind C and Tahara E :"Effect of hepatocyte growth factor on the expression of E-and P-cadherin in gastric carcinoma cell lines." Virchows Archic. 425. 139-144 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kuniyasu H,Yasui W,Yokozaki H,Akagi M,Akama Y,Kitahara K,Fujii K and Tahara E: "Frequent loss of heterozygosity of the long arm of chromosome 7 is closely associated with progression of human gastric carcinomas." Int.J.Cancer. 59. 597-600 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tahara E,Kuniyasu H,Yasui W and Yokozaki H.: "Abnormal expression of growth factors and their receptors in stomach cancer. Gann Monograph on" Cancer Research. 42. 163-173 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tahara E :"Cancer-stromal interaction through growth factor/cytokine networks implicated in growth of stomach cancer." Proceedings of the 24th International Symposium of the Princess Takamatsu Cancer Research Fund, Princeton Scientific Publishing Co., Inc., Princeton, New Jersey, U.S.A.187-194 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kuniyasu H,Yasui W,Akama Y,Akagi M,Tohdo M,Ji ZQ,Kitadai Y,Yokozaki H and Tahara E.: "Expression of cripto in human gastric carcinomas : an association with tumor stage and prognosis." J.Exp.Clin.Cancer Res.13 (2). 151-157 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Lotan R,Ito H,Yasui W,Yokozaki H,Lotan D and Tahara E: "Expression of a 31-kDa lactoside-binding lectin in normal human gastric mucosa and in primary and metastatic gastric carcinomas." Int.J.Cancer.56. 474-480 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ayhan A,Yasui W,Yokozaki H,Seto M,Ueda R and Tahara E.: "Loss of heterozygosity at the bcl-2 gene locus and expression of bcl-2 in human gastric and colorectal carcinomas." Jpn.J.Cancer Res.85. 584-591 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kozako Y,Yasui W,and Tahara E.: "Expression of beta1 integrin in human gastric carcinomas : correlation with histological type and tumor progression." Int.J.Oncology. 5. 225-230 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Saeki T,Salomon D,Normnno N,Johnson GR,Gullick WJ,Mandai K,Moriwaki S,Takashima S,Kuniyasu H,Tahara E,Kawami H,Nishiyama M and Toge T.: "Immunohistochemical detection of cripto-1, amphiregulin and transforming growth factor alpha in human gastric carcinomas and intestinal metaplasia." Int.J.Oncology. 5. 215-223 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tahara, E.: "Gene alterations in intestinal metaplasia and gastric cancer." European J.Gastroenterology & Hepatology. 6. S97-S101 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yokozaki H,Ito R,Nakayama H,Kuniyasu H,Taniyama K and Tahara E :"Expression of CD44 abnormal transcripts in human gastric carcinomas." Cancer Letters. 83. 229-234 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Horii A,Han H-J,Shimada M,Yanagisawa A,Kato Y,Ohta H,Yasui W,Tahara E and Nakamura Y :"Frequent replication errors at microsatellite loci in tumors of patients with multiple primary cancers." Cancer Research. 54. 3373-3375 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Sugimura T,Sugano H,Terada M,Stemmermann GN,Yasui W and Tahara E :"Meeting Report, First International Workshop of the Princess Takamatsu Cancer Research Fund : Intestinal Metaplasia and Gastric Cancer." Molecular Carcinogenesis. 11 (1). 1-7 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ito H and Tahara E.: "Endocrine cell tumor of the stomach." Gastric Cancer (ed.Nishi M,Ichikawa H,Nakajima T,Maruyama K and Tahara E).Springer-Verlag, Tokyo. 151-167 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tahara E,Yokozaki H and Yasui W.: "Growth factors in gastric cancer." Gastric Cancer (ed.Nishi M,Ichikawa H,Nakajima T,Maruyama K and Tahara E).Springer-Verlag, Tokyo. 209-217 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yasui W,Ayhan A,Kitadai Y,Nishimura K,Yokozali H: "its kinase activity in human gastric and colonic carcinomas." Int.J.Cancer. 53. 36-41 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nakayama H,Yasui W,Yokozaki H and Tahara E.: "Reduced expression of nm23 is associated with metastasis of human gastric carcinomas." Jpn.J.Cancer Res.84. 184-190 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tahara E.: "Molecular mechanism of stomach carcinogenesis." J.Cancer Res.Clin.Onco.119. 265-272 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tohdo H,Yokozaki H,Haruma K,Kajiyama G and Tahara E: "p53 gene multations in gastric adenomas." Virchows Archiv B (Cell Pathol). 63. 191-195 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yasui W,Sano T,Nishimura K,Kitadai Y,Ji Z-Q,Yokozaki H,Ito H and Tahara E.: "Expression of P-cadherin in gastric carcinomas and its reduction in tumor progression." Int.J.Cancer. 54. 49-52 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kitadai Y,Yamazaki H,Yasui W,Kyo E,Yokozaki H,Kajiyama G,Johnson AC,Pastan I and Tahara E.: "GC factor represses transcription of several growth factor/receptor genes and causes growth inhibition of human gastric carcinoma cell lines." Cell Growth & Differentiation. 4. 291-296 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yokozaki H,Ito M,Yasui W,Kyo E,Kuniyasu H,Kitadai Y,Tsubouchi H,Daikuhara Y and Tahara E: "Biologic effect of human hepatocyte growth factor on human gastric carcinoma cell lines." Int.J.Oncology. 3. 89-93 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kyo E,Yokozaki H,Yanagihara K,Yasui W,Ito M,Sano T,Lee PS,Saya H and Tahara, E.: "Reduced tumorigenicity and cell motility of a gastric carcinoma cell line by introduction of wild-type p53 gene." Int.J.Oncology. 3. 265-271 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kitadai Y,Yasui W,Yokozaki H,Kuniyasu H,Ayhan A,Haruma K,Kajiyama G,Johnson GR and Tahara E.: "Expression of amphiregulin, a novel gene of the epidermal growth factor family in human gastric carcinomas." Jpn.J.Cancer Res.84. 879-884 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kuniyasu H,Yasui W,Yokozaki H,Kitadai Y and Tahara E.: "A berrant expression of c-met mRNA in human gastric carcinomas." Int.J.Cancer. 55. 72-75 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ito R,Kitadai Y,Kyo E,Yokozaki H,Yasui W,Yamashita U,Nikai H and Tahara E.: "Interleukin 1alpha acts as an autocrine growth stimulator for human gastric carcinoma cells." Cancer Research. 53. 4102-4106 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ito M,Yasui W,Kyo E,Yokozaki H,Nakayama H,Ito H and Tahara E.: "Growth inhibition of transforming growth factor beta on human gastric carcinoma cells : Receptor and postreceptor signaling." Cancer Res.52. 295-300 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ito M,Yasui W,Nakayama H,Yokozaki H,Ito H and Tahara E.: "Reduced levels of transforming growth factor-beta type I receptor in human gastric carcinomas." Jpn.J.Cancer Res.83. 86-92 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kameda T,Yasui W,Tsujino T,Nakayama H,Ayhan A,Ito H and Tahara E.: "Tyrosine kinase activity of epidermal growth factor receptor in human gastric carcinomas." Path.Res.Pract.188. 37-43 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Mattar R,Yokozaki H,Yasui W,Ito H and Tahara E: "p53 gene mutations in gastric cancer cell lines." Oncol. (Life Sci.Adv.). 11. 7-12 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yokozaki H,Kuniyasu H,Kitadai Y,Nishimura K,Todo H,Ayhan A,Yasui W,Ito H and Tahara E.: "p53 point mutations in primary human gastric carcinomas." J.Cancer Res.Clin.Oncol.119. 67-70 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kuniyasu H,Yasui W,Kitadai Y,Yokozaki H,Ito H,Tahara E.: "Frequent amplification of the c-met gene in scirrhous type stomach cancer." Biochem.Biophys.Res.and Commun.189. 227-232 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kitadai Y,Yasui W,Yokozaki H,Kuniyasu H,Haruma K,Kajiyama G and Tahara E: "The level of a transcription factor Sp1 is correlated with the expression of EGF receptor in human gastric carcinomas." Biochem.Biophys.Res.Commun.189. 1342-1348 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nakatsuru S,Yanagisawa A,Ichii S,Tahara E,Kato Y,Nakamura Y and Horii A.: "Somatic mutation of the APC gene in gastric cancer : Frequent mutations in very well differentiated adenocarcinoma and signet ring cell carcinoma." Human Molecular Genetics. 1. 559-563 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Shimamoto T,Haruma K,Sumii K,Kajiyama G and Tahara E: "Flow cytometric DNA analysis of gastric smooth mucsle tumors." Cancer. 70. 2031-2034 (1992)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 1996-04-15  

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