K-ras mutation promotes colorectal carcinogenesis through GST-π

K-ras突变通过GST-π促进结直肠癌发生

• 批准号: 22590700
• 负责人: TAKAYAMA Tetsuji
• 金额: $ 2.91万
• 依托单位: The University of Tokushima
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2010
• 资助国家: 日本
• 起止时间: 2010 至 2012
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22590700/
• 关键词: 下部消化管学(小腸、大腸); 大腸癌; GST-π; RAF; JNK; K-ras; 大腸発癌; MAP kinase

We investigated the role of GST-πin growth promotion and apoptosis resistance of colorectal cancer. When a mutated K-ras gene was transfected into K-ras wild colon cancer cell line, GST-πexpression was induced. The transfectant cells showed enhanced growth promotion activity via RAF/MEK/ERK activation and apoptosis resistance by inhibited JNK and p53 pathway. In contrast, GST-πknockdown cells showed growth inhibition and apoptosis enhancement by the inverse action mechanisms. Immunoprecipitation revealed that GST-πwas directly interacted with RAF and JNK respectively. These results indicate that GST-π promote cell growth via direct binding to RAF and subsequent RAF/MEK/ERK activation, and inhibit apoptosis via direct binding to JNK and subsequent p53 apoptosis pathway.

我们研究了GST-π在大肠癌促生长和抗凋亡中的作用。将突变的K-ras基因转染到K-ras野生型结肠癌细胞系中，可诱导GST-π表达。转染细胞通过激活RAF/MEK/ERK表现出更强的促生长活性，通过抑制JNK和p53通路表现出更强的抗凋亡活性。而GST-π基因敲低的细胞则表现出相反的生长抑制和凋亡促进作用。免疫沉淀显示GST-π分别与RAF和JNK直接相互作用。这些结果表明GST-π通过直接结合RAF并随后激活RAF/MEK/ERK促进细胞生长，并通过直接结合JNK并随后激活p53凋亡途径抑制细胞凋亡。

项目成果

Colon cancer prevention targeting GST-π

针对 GST-π 的结肠癌预防

• 发表时间: 2011
• 作者: Shin Fujioka;Ikuo Nakamichi;Atsushi Hirano;Takayuki Matsumoto;Takayama T
• 通讯作者: Takayama T

A mechanism for abnormal angiogenesis in human radiation proctitis: analysis of expression profile for angiogenic factors

• DOI: 10.1007/s00535-011-0470-2
• 发表时间: 2012-01-01
• 期刊: JOURNAL OF GASTROENTEROLOGY
• 影响因子: 6.3
• 作者: Takeuchi, Hisashi;Kimura, Tetsuo;Takayama, Tetsuji
• 通讯作者: Takayama, Tetsuji

SSA/Pの拡大内視鏡所見と遺伝子異常の解析

SSA/P 放大内镜检查结果和遗传异常分析

• 发表时间: 2012
• 作者: Araki M;Aranami T;Matsuoka T;Nakamura M;Miyake S;Yamamura T.;岡本耕一
• 通讯作者: 岡本耕一

Clinical Benefit of High-Sensitivity KRAS Mutation Testing in Metastatic Colorectal Cancer Treated with Anti-EGFR Antibody Therapy

• DOI: 10.1159/000336792
• 发表时间: 2012-01-01
• 期刊: ONCOLOGY
• 影响因子: 3.5
• 作者: Kimura, Tetsuo;Okamoto, Koichi;Takayama, Tetsuji
• 通讯作者: Takayama, Tetsuji

Chemopreventive effect of RAS inhibitor on azoxymethane-induced colorectal carcinogenesis.

RAS 抑制剂对氧化偶氮甲烷诱导的结直肠癌的化学预防作用。

• 发表时间: 2012
• 作者: Tsuda M;Takayama T;et al
• 通讯作者: et al