Segregation of steroid receptor coactivator-1 from steroid receptors in mammary epithelium

Segregation of steroid receptor coactivator-1 from steroid receptors in mammary epithelium
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DOI:
10.1073/pnas.96.1.208
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发表时间:
1999-01-05
影响因子:
11.1
通讯作者:
Jeng, MH
Jeng, MH
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Shim, WS;DiRenzo, J;Jeng, MH

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类固醇受体辅激活因子-1(SRC-1)家族成员与类固醇受体(包括雌激素受体α(ER α)和孕酮受体(PR))相互作用以增强配体依赖性转录。然而,ER α和SRC-1的表达被发现在雌激素反应性大鼠乳腺上皮细胞内的不同细胞亚群中分离。这一发现与基质的发现相反,基质中大量细胞共表达ER α和SRC-1。雌激素处理的动物诱导PR表达的ER α-表达乳腺上皮细胞中的SRC-1的情况下,可检测到的,并没有影响SRC-1和ER α表达的分离模式。尽管ER α和SRC-1共表达,但雌激素处理在间质中既不表达也不诱导PR。这些结果表明SRC-1对于ER α介导的乳腺上皮细胞中PR的诱导不是必需的,并且对于同时表达ER α和SRC-1的间质细胞中PR的诱导也是不够的。此外,SRC-1在与表达ER α或PR的乳腺上皮细胞亚群不同的乳腺上皮细胞亚群中的表达提高了SRC-1具有细胞类型特异性功能的可能性,而不仅仅是作为乳腺上皮中ER α或PR的共激活剂。
Steroid receptor coactivator-1 (SRC-1) family members interact with steroid receptors, including estrogen receptor alpha (ER alpha) and progesterone receptor (PR), to enhance ligand-dependent transcription. However, the expression of ER alpha and SRC-1 was found to be segregated in distinct subsets of cells within the epithelium of the estrogen-responsive rat mammary gland. This finding was in contrast to the finding for the stroma, where significant numbers of cells coexpressed ER alpha and SRC-1. Treatment of animals with estrogen induced PR expression in the ER alpha-expressing mammary epithelial cells in the absence of detectable SRC-1 and did not affect the segregated pattern of SRC-1 and ER alpha expression. PR was neither expressed nor induced by estrogen treatment in stroma, despite the coexpression of ER alpha and SRC-1, These results suggest that SRC-1 is not necessary for ER alpha-mediated induction of PR in mammary epithelial cells and is also not sufficient, for PR induction in stromal cells expressing both ER alpha and SRC-1. Furthermore, the expression of SRC-1 in a subpopulation of mammary epithelial cells distinct from those expressing ER alpha or PR raises the possibility that SRC-1 has cell type-specific functions other than simply to act as coactivator for ER alpha or PR in the mammary epithelium.