Department of Urology, Innsbruck Medical University, Innsbruck, Austria.
Prostate. 2011 Mar 1;71(4):431-7. doi: 10.1002/pros.21257. Epub 2010 Sep 21.
Steroid receptor coactivators p300 and CBP are highly expressed in advanced prostate cancer. They potentiate activation of androgen receptor by androgens and anti-androgens. In the present study, we have addressed the question whether these coactivators enhance activity of estrogen receptor-beta (ER-β), which is variably expressed in prostate cancers.
Expression levels of the coactivators p300 and CBP were manipulated by plasmid or siRNA transfections and activity of ER-β was measured by luciferase assays. Viability was measured by MTT assays and cellular migration was determined by wound-healing and Boyden chamber assays.
High expression of ER-β was found in PC3 cells which were used for the experiments. p300 or CBP enhanced activation of ER-β by genistein. Antiestrogens did not acquire agonistic properties in the presence of increased concentrations of either coactivator. Inhibition of p300 or CBP decreased genistein stimulation of ER-β. Genistein reduced migration of PC3 prostate cancer cells and down-regulation of p300 potentiated this effect.
p300 and CBP are implicated in regulation of ER-β activity and cellular migration in prostate cancer. These findings are important for understanding of action of ER-β in carcinoma of the prostate.
类固醇受体共激活因子 p300 和 CBP 在晚期前列腺癌中高度表达。它们增强雄激素和抗雄激素对雄激素受体的激活作用。在本研究中，我们探讨了这些共激活因子是否增强了雌激素受体-β（ER-β）的活性，而 ER-β在前列腺癌中表达情况不一。
通过质粒或 siRNA 转染来操纵共激活因子 p300 和 CBP 的表达水平，并通过荧光素酶测定法来测量 ER-β 的活性。通过 MTT 测定法来测量细胞活力，通过划痕愈合和 Boyden 室测定法来确定细胞迁移。
实验中使用的 PC3 细胞中发现 ER-β 高表达。p300 或 CBP 增强了金雀异黄素对 ER-β 的激活作用。在增加浓度的共激活因子存在下，抗雌激素并未获得激动剂特性。抑制 p300 或 CBP 降低了金雀异黄素对 ER-β 的刺激作用。金雀异黄素减少了 PC3 前列腺癌细胞的迁移，而下调 p300 增强了这种作用。
p300 和 CBP 参与调节前列腺癌中 ER-β 的活性和细胞迁移。这些发现对于理解 ER-β 在前列腺癌中的作用非常重要。
