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Endogenously expressed estrogen receptor and coactivator AIB1 interact in MCF-7 human breast cancer cells

机译:内源性表达的雌激素受体和 共激活因子AIB1在MCF-7人乳腺癌细胞中相互作用

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摘要

Coactivators are believed to mediate estrogen-induced gene responses via interaction with estrogen receptors (ER). Currently, a major challenge is to determine the importance of each coactivator in a specific cell type and promoter context in response to a particular ligand. The potential of ER to interact with a growing list of coactivators has been shown in a variety of in vitro and gene transfer assays, yet very few data have demonstrated the interaction of endogenous coactivators with ER in intact cells. We report here a ligand-specific interaction of endogenous human ER (hER) and the AIB1 coactivator in MCF-7 human breast cancer cells by using immunoprecipitation analyses. Complexes between endogenously expressed hER and AIB1 were detected in estradiol-treated cells and to a much lesser extent in cells treated with the partial agonist, monohydroxytamoxifen. We were unable to detect an hER–SRC-1 complex in our immunoprecipitations from MCF-7 cells. The in vitro-binding affinity for mouse ER interaction with AIB1 was estimated to be 40–120 nM. We conclude that AIB1 is a major coactivator for hER in MCF-7 human breast cancer cells.
机译:据认为,共激活因子可通过与雌激素受体(ER)相互作用介导雌激素诱导的基因应答。当前,主要的挑战是确定每种共激活剂在特定细胞类型和启动子环境中响应特定配体的重要性。在各种体外和基因转移试验中均显示了ER与越来越多的共激活因子相互作用的潜力,但很少有数据证明完整细胞中内源共激活因子与ER相互作用。我们在这里报告通过使用免疫沉淀分析的内源性人内质网(hER)和MCF-7人乳腺癌细胞中AIB1共激活因子的配体特异性相互作用。在雌二醇处理的细胞中检测到内源性表达的hER和AIB1之间的复合物,在用部分激动剂单羟基他莫昔芬处理的细胞中检测到的复合物的程度要小得多。我们无法从MCF-7细胞的免疫沉淀物中检测到hER–SRC-1复合物。小鼠ER与AIB1相互作用的体外结合亲和力估计为40-120 nM。我们得出的结论是 AIB1是MCF-7人乳腺癌细胞中hER的主要共激活因子。

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