1992 Fiscal Year Annual Research Report

ヒト胃癌の発生・増殖・進展に関与する増殖因子関連遺伝子・癌抑制遺伝子の解折

Research Project

Project/Area Number	04404030
Research Institution	Hiroshima University
Principal Investigator	田原榮一広島大学, 医学部, 教授 (00033986)
Co-Investigator(Kenkyū-buntansha)	国安弘基広島大学, 医学部, 助手横崎宏広島大学, 医学部, 講師 (10200891) 安井弥広島大学, 医学部, 助教授 (40191118)
Keywords	胃癌 / HGF / c-met / p53遺伝子 / APC遺伝子 / bc1-2 / TGFβレセプター / K-sam / cripto
Research Abstract	ヒト胃癌の発生・増殖・進展には、多種の癌遺伝子・癌抑制遺伝子の変化と多種の増殖因子・受容体系の異常発現が関与するが、高分化腺癌と低分化腺癌との間には共通した遺伝子異常(c-met,p53)と違った遺伝子異常とが存在する。従って、高分化腺癌と低分化腺癌とは異なったgenetic pathwayを有するものと考えられる。即ち、高分化腺癌の場合には、telomereの減少、2.2kb遺伝子欠失が腸上皮化生に発生し、それにp53やAPC遺伝子の変異、criptoの過剰発現が加わり、そしてAPCとp53遺伝子の欠失、c-met遺伝子異常発現、bc1-2の欠失など、復数の遺伝子変化が蓄積することによって癌が発生してくると考えられる。その場合、腸上皮化生から腺腫を経て癌化するものは大腸癌過程とよく似た遺伝子異常を示す。更に、その進展には1q,18q(DCC)の欠失、TGFβ_1受容体の減少・消失の組合せが必要であり、その内、C-erdβ-2過剰発現クローンは転移を示す。他方、低分化腺癌の場合には、p53とc-metの遺伝子異常が癌化に大きく関与し、その進展には接着分子の消失、1pの欠失、TGFβ_1受容体の消失が加わり、その内、TGFβの過剰発現、c-metあるいはK-sam遺伝子の増幅を示すクローンはスキルスへと進展あるいは転移形成を示すと考えられる。低分化腺癌のgenetic pathwayは食道や大腸の発癌機構とは明らかに異なっている。又、p53変異のスペクトルからみると、高分化腺癌ではA:Tの変異が頻発するのに対して低分化腺癌ではG:CからA:Tへの変換が主体である。従って、2つの組織型の発生には異なった発癌因子あるいは背景因子が存在すると考えられ、前者では萎縮性胃炎、アルコール、ウレタンなどが、後者では、N-nitrosoaminesなどがあげられる。

Research Products

(14 results)

All Other

All Publications (14 results)

[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. (1993)
[Publications] Tahara E: "Molecular mechanism of stomach carcinogenesis." J.Cancer Res.Clin.Oncol.119. 119-272 (1993)
[Publications] Yasui W: "Increased expression of p34^<odo2> and its kinase activity in human gastric and colonic carcinomas." Int.J.Cancer. 53. 36-41 (1993)
[Publications] Kitadai Y: "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)
[Publications] Yasui W: "Expression of transforming growth factor alpha in human tissues:immunohistochemical study and Northern blot analysis." Virchows Archiv A. 421. 513-519 (1992)
[Publications] Yokozaki H: "p53 point mutations in primary human gastric carcinomas." J.Cancer Res.Clin.Oncol.119. 67-70 (1992)
[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)
[Publications] Kuniyasu H: "Frequent amplification of the c-met gene in scirrhous type stomach cancer." Biochem.Biophys.Res.Commun.189. 227-232 (1992)
[Publications] Mattar R: "p53 gene mutations in gastric cancer cell lines." Oncol.(Life Sci.Adv.). 11. 7-12 (1992)
[Publications] Kameda T: "Tyrosine kinase activity of eqidermal growth factor receptor in human gastric carcinomas." Path. Res.Pract.188. 37-43 (1992)
[Publications] Ito M: "Growth inhibition of transforming growth factor β on human gastric carcinoma cells:receptor and postreceptor signaling." Cancer Research. 52. 295-300 (1992)
[Publications] Ito M: "Reduced levels of transforming growth factor-beta type I receptor in human gastric carcinomas." Jpn.J.Cancer Res.83. 86-92 (1992)
[Publications] Yasui W: "Surgica6 Gynecologic Oncology Ediyed by E.Burghardt" Thieme Medical Publishers,Inc.New York, 729 (1993)
[Publications] Yasui W: "Diagnostic Molecular Pathology Edited by C.S.Herrington and J.O'.D.McGee" Owford University Press, 218 (1992)

1992 Fiscal Year Annual Research Report

ヒト胃癌の発生・増殖・進展に関与する増殖因子関連遺伝子・癌抑制遺伝子の解折

Principal Investigator

田原 榮一 広島大学, 医学部, 教授 (00033986)

Research Products

[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. (1993)

[Publications] Tahara E: "Molecular mechanism of stomach carcinogenesis." J.Cancer Res.Clin.Oncol.119. 119-272 (1993)

[Publications] Yasui W: "Increased expression of p34^<odo2> and its kinase activity in human gastric and colonic carcinomas." Int.J.Cancer. 53. 36-41 (1993)

[Publications] Kitadai Y: "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)

[Publications] Yasui W: "Expression of transforming growth factor alpha in human tissues:immunohistochemical study and Northern blot analysis." Virchows Archiv A. 421. 513-519 (1992)

[Publications] Yokozaki H: "p53 point mutations in primary human gastric carcinomas." J.Cancer Res.Clin.Oncol.119. 67-70 (1992)

[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)

[Publications] Kuniyasu H: "Frequent amplification of the c-met gene in scirrhous type stomach cancer." Biochem.Biophys.Res.Commun.189. 227-232 (1992)

[Publications] Mattar R: "p53 gene mutations in gastric cancer cell lines." Oncol.(Life Sci.Adv.). 11. 7-12 (1992)

[Publications] Kameda T: "Tyrosine kinase activity of eqidermal growth factor receptor in human gastric carcinomas." Path. Res.Pract.188. 37-43 (1992)

[Publications] Ito M: "Growth inhibition of transforming growth factor β on human gastric carcinoma cells:receptor and postreceptor signaling." Cancer Research. 52. 295-300 (1992)

[Publications] Ito M: "Reduced levels of transforming growth factor-beta type I receptor in human gastric carcinomas." Jpn.J.Cancer Res.83. 86-92 (1992)

[Publications] Yasui W: "Surgica6 Gynecologic Oncology Ediyed by E.Burghardt" Thieme Medical Publishers,Inc.New York, 729 (1993)

[Publications] Yasui W: "Diagnostic Molecular Pathology Edited by C.S.Herrington and J.O'.D.McGee" Owford University Press, 218 (1992)

田原榮一広島大学, 医学部, 教授 (00033986)