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

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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.