Investigation of chromatin remodeling by histone modifier protein in carcinogenesis and progression.

组蛋白修饰蛋白在癌发生和进展中染色质重塑的研究。

• 批准号: 21590453
• 负责人: FUJII Satoshi
• 金额: $ 3万
• 依托单位: National Cancer Center Research Institute and Research Center for Innovative Oncology, National Cancer Center Hospital East
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2009
• 资助国家: 日本
• 起止时间: 2009 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21590453/
• 关键词: 腫瘍; ヒストン; クロマチン; がん

It is demonstrated that MEK-ERK1/2-Elk-1 pathway leads to EZH2 overexpression. The triple-negative and ERBB2-overexpressing subtypes of breast cancer are known to contain more rapidly proliferating breast cancer cells. The signaling pathway connected to EZH2 overexpression was associated with both aggressive subtypes of breast cancer, showing one of the clinicopathological significance of overexpression of histone modifier protein. The oncogenic role of EZH2, a histone modifier protein that is induced by oncogenic mutant RAS is also defined in pancreatic carcinogenesis, using pancreatic cancers of transgenic rats exogenously expressing human mutant RAS. That is, EZH2 was found to be a real effecter protein in the downstream of the MEK-ERK pathway in pancreatic carcinogenesis.

已经证明MEK-ERK 1/2-Elk-1通路导致EZH 2过表达。已知乳腺癌的三阴性和ERBB 2过表达亚型含有更快速增殖的乳腺癌细胞。与EZH 2过表达相关的信号通路与乳腺癌的两种侵袭性亚型相关，显示了组蛋白修饰蛋白过表达的临床病理学意义之一。EZH 2是一种由致癌突变型RAS诱导的组蛋白修饰蛋白，其致癌作用也在胰腺癌发生中被定义，使用外源表达人突变型RAS的转基因大鼠的胰腺癌。也就是说，发现EZH 2是胰腺癌发生中MEK-ERK通路下游的真实的效应蛋白。

项目成果

MEK-ERK pathway regulates EZH2 overexpression in association with aggressive breast cancer subtypes

• DOI: 10.1038/onc.2011.118
• 发表时间: 2011-09-01
• 期刊: ONCOGENE
• 影响因子: 8
• 作者: Fujii, S.;Tokita, K.;Ochiai, A.
• 通讯作者: Ochiai, A.

活性酸素種によるヒストン修飾蛋白の発現誘導

活性氧诱导组蛋白修饰蛋白的表达

• 发表时间: 2010
• 作者: 石井さなえ;稲葉宗夫;武井史郎;河村則子;千葉陽一;細川昌則;島田厚良;小林真季
• 通讯作者: 小林真季

ヒストン修飾蛋白によるがんの発生及び進展機構の解明

阐明组蛋白修饰蛋白引起的癌症发生和进展的机制

• 发表时间: 2010
• 作者: Toma H;Hatabu T;Vanisaveth V;Mannoor MK;Watanabe H;Li C;Kobayashi. J. Phompida S;Kano S;Sato Y;藤井誠志
• 通讯作者: 藤井誠志

Aberrant expression of EZH2 is associated with a poor outcome and P53 alteration in squamous cell carcinoma of the esophagus

• DOI: 10.3892/ijo.2010.868
• 发表时间: 2011-02-01
• 期刊: INTERNATIONAL JOURNAL OF ONCOLOGY
• 影响因子: 5.2
• 作者: Yamada, Atsushi;Fujii, Satoshi;Ochiai, Atsushi
• 通讯作者: Ochiai, Atsushi

The significance of histone variants in cancer cells.がん細胞におけるヒストン変異体の意義

癌细胞中组蛋白变异的重要性。

• 发表时间: 2011
• 作者: Takei;S.;Tokuhira;Y.;Shimada;A.;Hosokawa;M.;Fukuoka;S.;藤井誠志
• 通讯作者: 藤井誠志