Mechanism of Fas-mediated apoptosis in p53-transfected human colon carcinoma cells (WiDr)

Fas 介导 p53 转染人结肠癌细胞凋亡的机制 (WiDr)

• 批准号: 07670590
• 负责人: AOYAMA Nobuo
• 金额: $ 1.47万
• 依托单位: Kobe University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1996
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07670590/
• 关键词: p53; apoptosis; replication error; colorectal carcinoma; multidrug resistance; apoptosis; p53

To investigate the biological function of p53 in colon carcinoma cells, a wild-type p53 expression plasimid under the control of the human cytomegalovirus promotor was stably transfected into the human colon adenocarcinoma cell line WiDr.Wild-type p53+ cells which were incubated with anti-Fas IgM showed marked cytolysis with preferential overexpression of wild-type p53 accompanied by overexpression of cyclin-dependent kinase inhibitor, WAF1. This model should help elucidating the additional role of the p53 tumor suppressor gene and the mechanism of apoptosis in colon carcinoma cells.Replication error (RER), apoptosis and p53 abnormality were analyzed in surgically resected 60 colorectal cartinoma tissues. Positive RER was evaluated that RER was observed at least one locus among five microsatellite makers, and p53 and apoptosis were evaluated by immunohistochemical study. The incidence of RER positive colorectal cancer was 15% (nine cases), and the age of the RER potitive patients was younger than that of RER negative ones, however, the index of apoptosis was not different between positive or negative of RER and p53 abnormality.

为了研究p53在结肠癌细胞中的生物学功能，将人巨细胞病毒启动子控制下的野生型p53表达质粒稳定转染到人结肠腺癌细胞系WiDr中。与抗Fas IgM一起孵育的野生型p53+细胞表现出明显的细胞溶解，并优先过表达野生型p53 伴随着细胞周期蛋白依赖性激酶抑制剂 WAF1 的过度表达。该模型应有助于阐明p53抑癌基因的额外作用以及结肠癌细胞凋亡的机制。对手术切除的60个结直肠癌组织中的复制错误（RER）、凋亡和p53异常进行了分析。阳性RER评价为5个微卫星标记中至少观察到1个位点的RER，并通过免疫组化研究评价p53和细胞凋亡。 RER阳性结直肠癌发病率为15%（9例），RER阳性患者年龄较RER阴性患者年轻，但RER阳性、阴性及p53异常者的细胞凋亡指数无差异。

项目成果

Tamura T,Aoyama N et al: "Induction of Fas-mediated apoptosis in p53-transfected human colon carcinoma cells." Oncogene. 11. 1939-946 (1995)

Tamura T,Aoyama N 等人：“在 p53 转染的人结肠癌细胞中诱导 Fas 介导的细胞凋亡。”

Takahashi R, Maeda S. et al: "Trangfection of wild-type TP53 indices diffeventiation in human gingival cavcinoma cells" Euv J Cancev. 32A. 533-539 (1996)

Takahashi R、Maeda S. 等人：“野生型 TP53 的转染指数在人牙龈海绵瘤细胞中的分化”Euv J Cancev。

Tamura T, Aoyama N et al: "Induction of Fas-mediatid apoptosis in p53-trasisfectel human color cavcinoma cell3" Oncogene. 11. 1939-1946 (1995)

Tamura T、Aoyama N 等人：“p53-trasisfectel 人彩色静脉瘤细胞 3 中 Fas 介导细胞凋亡的诱导”癌基因。

田村 孝雄, 青山 伸郎 他: "癌抑制遺伝子の生物学" GI veseavch. 3. 284-291 (1995)

Takao Tamura、Nobuo Aoyama 等：“肿瘤抑制基因的生物学”GI veseavch. 3. 284-291 (1995)

Takahashi R,Maeda S et al: "Transfection of wild-type TP53 induces differentiation in human gingival carcinoma cells." Eur J Cancer. 32A. 533-539 (1996)

Takahashi R、Maeda S 等人：“野生型 TP53 的转染可诱导人牙龈癌细胞分化。”