STEROID-HORMONE RECEPTORS COMPETE FOR FACTORS THAT MEDIATE THEIR ENHANCER FUNCTION
STEROID-HORMONE RECEPTORS COMPETE FOR FACTORS THAT MEDIATE THEIR ENHANCER FUNCTION
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DOI：
10.1016/0092-8674(89)90918-5
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发表时间：
1989-05-05
期刊：
影响因子：
64.5
通讯作者：
CHAMBON, P
中科院分区：
文献类型：
--
作者：
MEYER, ME;GRONEMEYER, H;CHAMBON, P
孕激素受体（PR）的报告基因的转录刺激被抑制在转染的HeLa细胞共表达雌激素受体（ER）的ER剂量和雌激素依赖性的方式。这两个N-末端A/B区域和ER的激素结合结构域都参与了这种抑制，这是拮抗抗雌激素，并没有出现涉及ER和报告基因或PR之间的直接相互作用。ER表达也抑制激活的糖皮质激素受体（GR），PR和GR表达抑制激活ER，虽然在较低程度上。在用ER报告基因转染的T47 D和MCF-7乳腺癌细胞中存在的内源性PR和ER之间观察到类似的转录干扰。此外，常驻雌激素诱导的pS2基因的转录被部分抑制暴露MCF-7细胞孕激素或糖皮质激素。我们认为这些观察结果反映了对功能限制性转录因子的竞争。
Stimulation of transcription of reporter genes by the progesterone receptor (PR) was inhibited in transfected HeLa cells by co-expressing the estrogen receptor (ER) in an ER-dose- and estrogen-dependent manner. Both the N-terminal A/B region and the hormone binding domain of ER were involved in this inhibition, which was antagonized by antiestrogens and did not appear to involve direct interaction between ER and either reporter gene or PR. ER expression also inhibited activation by the glucocorticoid receptor (GR), and both PR and GR expression inhibited activation by ER, albeit to a lower extent. Similar transcriptional interference was observed between the endogenous PR and ER present in T47D and MCF-7 breast cancer cells transfected with an ER reporter gene. Moreover, transcription of the resident estrogen-induced pS2 gene was partially inhibited by exposing MCF-7 cells to progestins or glucocorticoids. We propose that these observations reflect competition for a functionally limiting transcription factor(s).