The role of the nuclear receptors in cancer development

选择性雌激素受体调节剂(SERM)是一种成熟的治疗激素依赖性癌症的药物，如乳腺癌、子宫内膜癌和卵巢癌。SERM Liganded-ERα以组织特异性方式调节其靶基因。然而，决定组织特异性的分子机制还不是很清楚。我们使用生化纯化技术来鉴定依赖于α的ER相关蛋白。有趣的是，我们发现含有溴结构域的蛋白BRD4在靶基因启动子上招募正转录延伸因子b(P-TEFb)并刺激转录延伸。

Selective estrogen receptor modulator (SERM) is a well-established agent in the management of hormone-dependent cancer such as breast, endometrial and ovarian cancer. SERM liganded-ERα regulates its target genes in tissue specific manner. However, the molecular mechanism which determines the tissue specificity is not well-known. We used biochemical purification techniques to identify ERα-associated proteins dependently on SERM. Interestingly, we found that bromodomain-containing protein BRD4, which is known to recruit positive transcription elongation factor b (P-TEFb) on target gene promoters and stimulates transcriptional elongation.