Shim W S, DiRenzo J, DeCaprio J A, Santen R J, Brown M, Jeng M H
Department of Internal Medicine, Division of Hematology/Oncology, University of Virginia Health Sciences Center, Charlottesville, VA 22908, USA.
Proc Natl Acad Sci U S A. 1999 Jan 5;96(1):208-13. doi: 10.1073/pnas.96.1.208.
Steroid receptor coactivator-1 (SRC-1) family members interact with steroid receptors, including estrogen receptor alpha (ERalpha) and progesterone receptor (PR), to enhance ligand-dependent transcription. However, the expression of ERalpha 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 ERalpha and SRC-1. Treatment of animals with estrogen induced PR expression in the ERalpha-expressing mammary epithelial cells in the absence of detectable SRC-1 and did not affect the segregated pattern of SRC-1 and ERalpha expression. PR was neither expressed nor induced by estrogen treatment in stroma, despite the coexpression of ERalpha and SRC-1. These results suggest that SRC-1 is not necessary for ERalpha-mediated induction of PR in mammary epithelial cells and is also not sufficient for PR induction in stromal cells expressing both ERalpha and SRC-1. Furthermore, the expression of SRC-1 in a subpopulation of mammary epithelial cells distinct from those expressing ERalpha or PR raises the possibility that SRC-1 has cell type-specific functions other than simply to act as coactivator for ERalpha or PR in the mammary epithelium.
类固醇受体辅激活因子-1(SRC-1)家族成员与类固醇受体相互作用,包括雌激素受体α(ERα)和孕激素受体(PR),以增强配体依赖性转录。然而,在雌激素反应性大鼠乳腺上皮内不同的细胞亚群中,发现ERα和SRC-1的表达是分离的。这一发现与基质中的情况相反,在基质中有大量细胞同时表达ERα和SRC-1。用雌激素处理动物,在未检测到SRC-1的情况下,可诱导表达ERα的乳腺上皮细胞中PR的表达,且不影响SRC-1和ERα表达的分离模式。尽管ERα和SRC-1共同表达,但雌激素处理在基质中既不诱导PR表达也不使其表达。这些结果表明,SRC-1对于乳腺上皮细胞中ERα介导的PR诱导不是必需的,对于同时表达ERα和SRC-1的基质细胞中的PR诱导也不充分。此外,在不同于表达ERα或PR的乳腺上皮细胞亚群中SRC-1的表达增加了一种可能性,即SRC-1除了在乳腺上皮中作为ERα或PR的辅激活因子发挥作用外,还具有细胞类型特异性功能。