The role of co-factor of estrogen receptor alfa in breast cancer cells

雌激素受体α辅助因子在乳腺癌细胞中的作用

• 批准号: 14571149
• 负责人: TOYAMA Tatsuya
• 金额: $ 2.24万
• 依托单位: Aichi Cancer Center Research Institute (2003)Nagoya City University (2002)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14571149/
• 关键词: beast cancer; estrogen receptor alfa

The ING1 gene was originally cloned as a candidate tumor suppressor of human breast cancer, and recent studies suggest that ING1 proteins are involved in chromatin remodeling functions via physical association with both histone acetyltransferases and histone deacetylases. In this study, we investigated whether p33^<ING1b>, one of the major ING1 isoforms, modulated the transcriptional activity of estrogen receptor (ER) a. In Cos-7 cells transfected with increasing in a dose-dependent manner. As p33^<ING1b> expression levels increased, transcription of an ER-responsive reporter gene by either estrogen-inducible full-length ERa or activation function (AF) 1 deletion mutant was enhanced, while the AF2 deletion mutant was unaffected by the presence of p33^<ING1b>. These results showed that p33^<ING1b> enhanced estrogen-induced ERa activity through the AF2 domain. Our data also demonstrated that the antiestrogens inhibited the transcriptional activity of ERa as stimulated by p33^<ING1b>. Furthermore, a weak physical association was observed between in vitro translated p33^<ING1b> and ERa. Our data presented here demonstrate that p33^<ING1b> acts like a coactivator for ERa and stimulates estrogen-induced ERa transcriptional activity consistent with a function for p33^<ING1b> in chromatin remodeling.

ING 1基因最初被克隆为人类乳腺癌的候选肿瘤抑制基因，最近的研究表明，ING 1蛋白通过与组蛋白乙酰转移酶和组蛋白去乙酰化酶的物理关联参与染色质重塑功能。在这项研究中，我们研究了P33^<ING1b>（主要的ING 1亚型之一）是否调节雌激素受体（ER）a的转录活性。在Cos-7细胞中转染后呈剂量依赖性增加。随着p33 α<ING1b>表达水平的增加，雌激素诱导的全长ER α或激活功能（AF）1缺失突变体对ER应答报告基因的转录增强，而AF 2缺失突变体不受p33 α存在的影响<ING1b>。这些结果表明，p33 α<ING1b>通过AF 2结构域增强雌激素诱导的ER α活性。我们的数据还表明，抗雌激素抑制由p33 α刺激的ER α的转录活性<ING1b>。此外，在体外翻译的p33 α和ER α之间观察到弱的物理关联<ING1b>。我们的数据表明，p33 α<ING1b>的作用类似于ER α的共激活因子，并刺激雌激素诱导的ER α转录活性，这与p33 α<ING1b>在染色质重塑中的功能一致。

项目成果

Toyama T, et al.: "p33ING1b stimulates the transcriptional activity of the estrogen receptor alfa via its activation function (AF) 2 domain"J Steroid Biochem Mol Biol. 87(1). 57-63 (2003)

Toyama T 等人：“p33ING1b 通过其激活功能 (AF) 2 结构域刺激雌激素受体 alfa 的转录活性”J Steroid Biochem Mol Biol。

Toyama T, et al.: "p33ING1b stimulates the transcriptional activity of the estrogen receptor a via its activation function (AF) 2 domain"Journal of Steroid Biochemistry and Molecular Biology. 87・1. 57-63 (2003)

Toyama T等：“p33ING1b通过其激活功能(AF)2结构域刺激雌激素受体a的转录活性”类固醇生物化学和分子生物学杂志87·1(2003)。

Toyama T, et al.: "p33ING1b stimulates the transcriptional activity of the estrogen receptor alfa via its activation function (AF) 2 domain"Journal of Steroid Biochemistry and Molecular Biology. 87・1. 57-63 (2003)

Toyama T等人：“p33ING1b通过其激活功能(AF)2结构域刺激雌激素受体α的转录活性”类固醇生物化学和分子生物学杂志87·1(2003)。