类固醇激素受体竞争的是介导其增强功能的因素
M E Meyer1, H Gronemeyer, B Turcotte
1Laboratoire de Génétique Moléculaire des Eucaryotes du CNRS, Strasbourg, France.
Cell
|May 5, 1989
概括
雌激素受体 (ER) 抑制HeLa细胞中的孕激素受体 (PR) 活性. 激素受体之间的这种交叉对话表明,对必要的转录因子进行竞争,影响基因表达.
科学领域:
- 分子内分泌学分子内分泌学
- 基因规则 基因规则
- 激素受体相互作用
背景情况:
- 孕激素受体 (PR) 和雌激素受体 (ER) 是调节基因转录的关键核受体.
- 不同的核受体之间的交叉交谈可以影响细胞对激素的反应.
研究的目的:
- 研究雌激素受体 (ER) 对孕激素受体 (PR) 中介基因转录的抑制作用.
- 探索ER,PR和葡萄糖皮质体受体 (GR) 之间的转录干扰的机制和程度.
主要方法:
- 用记者基因和PR和ER的表达载体感染HeLa细胞.
- 同表达研究以评估受体相互作用和转录活性.
- 乳腺癌细胞系内源性受体相互作用的分析 (T47D,MCF-7).
主要成果:
- 以剂量和雌激素为依赖的方式,ER显著抑制了PR刺激的记者基因转录.
- 无论是ER的N端A/B区域还是激素结合域都与抑制有关.
- 此外,ER还抑制了葡萄糖皮质体受体 (GR) 活性,PR/GR抑制了ER活性.
- 在乳腺癌细胞中观察到内源性PR和ER之间的转录干扰,影响pS2基因表达.
结论:
- 雌激素受体 (ER) 积极干扰孕激素受体 (PR) 和葡萄糖皮质体受体 (GR) 的转录活性.
- 这些发现表明,核受体可能在限制转录因子方面竞争,从而导致交叉对话和基因表达的调制.
- 这种受体交叉对话对理解激素驱动的过程有影响,特别是在乳腺癌中.
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