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

ING1基因最初被克隆为人类乳腺癌的候选肿瘤抑制因子，最近的研究表明，ING1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>， ING1的主要亚型之一，是否以剂量依赖的方式调节雌激素受体（ER） a在Cos-7细胞中的转录活性。随着p33^<ING1b>表达水平的增加，雌激素诱导的全长ERa或激活功能（AF） 1缺失突变体对er反应性报告基因的转录增强，而AF2缺失突变体不受p33^<ING1b>存在的影响。这些结果表明p33^<ING1b>通过AF2结构域增强雌激素诱导的ERa活性。我们的数据还表明，抗雌激素抑制了p33^<ING1b>刺激的ERa的转录活性。此外，在体外翻译的p33^<ING1b>和ERa之间观察到微弱的物理关联。我们在这里提出的数据表明，p33^<ING1b>像ERa的辅助激活因子一样，刺激雌激素诱导的ERa转录活性，这与p33^<ING1b>在染色质重塑中的功能一致。

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.