臨牀消化器内科 Vol.12 No.6(4)


特集名 分子生物学と消化管
題名 胃癌とアポトーシスの分子生物学
発刊年月 1997年 06月
著者 石田 雅人 鳥取大学医学部第一病理学教室
著者 井藤 久雄 鳥取大学医学部第一病理学教室
【 要旨 】 ヒト胃癌の発生,増殖,進展の過程においては多種多様な遺伝子変異が蓄積される.高分化腺癌と低分化腺癌ではp53に代表される共通した遺伝子変異と,c-erbB2やK-samなど両者で異なる遺伝子変異がある.胃癌細胞には増殖活性の亢進とともにアポトーシスが種々の程度に誘発される.アポトーシス細胞の比率は低分化腺癌よりも高分化腺癌で有意に高い.p53遺伝子変異陽性症例では陰性例に比較してアポトーシス細胞の比率が有意に低い.したがって,胃癌細胞のアポトーシスは細胞回転依存性と非依存性の経路が存在するとみなされる.術前5-FU投与は胃癌細胞のアポトーシスを有意に増加させる.p53遺伝子変異のない胃癌培養細胞株MKN-74では5-FU添加によりアポトーシスが誘発されるが,このとき,p21/waf1およびbaxが発現する.アポトーシスのシグナル伝達経路が解明されれば,胃癌治療の新しい展開が期待される.
Theme Molecular Biology & GI Tract
Title Molecular Biology of Human Gastric Carcinoma and Apoptosis
Author Masato Ishida First Department of Pathology, Faculty of Medicine, Tottori University
Author Hisao Ito First Department of Pathology, Faculty of Medicine, Tottori University
[ Summary ] A variety of gene alterations accumulate in the carcinogenesis, proliferation and progression of human gastric carcinomas. There are gene alterations, such as p53 gene and various alterations such as c-erbB2 and K-sam, which exist in both well and poorly differentiated carcinomas. Gastric cancer cells show increasing proliferative activity, along with the induction of apoptosis. The apoptotic index(AI) is significantly higher in well differentiated than in poor1y differentiated carcinomas. AI was significantly lower in carcinomas carrying the p53 gene mutation than in those without this mutation. These observations imply that apoptosis may occur in both a cell-cycle-dependent and an independent manner. Preoperative 5FU administration significantly enhanced apoptosis of gastric cancer cells as compared with controls(p<0.05). A human gastric cancer cell line, MKN-74, without the p53 gene mutation was induced to undergo apoptosis by 1 mM 5FU, in the process of which p21/waf1 and bax protein showed higher expression levels. Clarification of the signal transduction involved in apoptosis may allow the development of the new strategies for the treatment of human gastric carcinomas.
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