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首页> 美国政府科技报告 >Regulation of Estrogen-Responsive Gene Expression and Tumor Suppression by Transcriptional Cofactors
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Regulation of Estrogen-Responsive Gene Expression and Tumor Suppression by Transcriptional Cofactors

机译：转录辅助因子调节雌激素反应基因表达和抑制肿瘤

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TIP30 is a tumor suppressor that promotes apoptosis and inhibits angiogensis through the regulation of transcription. We previously found that TIP30 interacts with an ERalpha-interacting coactivator CIA (Coativator Independent of AF2). We propose to determine the effects of TIP30 and CIA on expression of ERalpha-responsive genes, such as c-Myc and Cyclin D1 in the first year. Now, we demonstrate that TIP30 and CIA are dynamically associated with transcription initiation and elongation complexes in response to estrogen. TIP30 overexpression represses ERalpha-mediated c-myc transcription, whereas TIP30 deficiency enhances c-myc transcription in the absence and presence of estrogen. Ectopic CIA cooperates with TIP30 to repress ERalpha-mediated c-myc transcription. Overexpression of CIA in ER-negative MDA- MB-231 cells induces apoptosis whereas overexpression of TIP30 does not. However, overexpression of both TIP30 and CIA in MDA-MB-231 cells effectively induce apoptosis. Therefore, our data suggest that TIP30 and CIA act as negative regulators to control transcription of genes including c-myc and cyclin D1 thereby suppressing tumor development. Thus, human Tip30 and CIA may represent new valuable diagnostic and therapeutic targets for anti-breast cancer therapy.

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