Prostate, 2011, 71(4):431-7.

Transcriptional Coactivators p300 and CBP Stimulate Estrogen Receptor-Beta Signaling and Regulate Cellular Events in Prostate Cancer

Jan Bouchal, et al

Department of Urology, Innsbruck Medical University, Innsbruck, Austria

BACKGROUND: 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.

METHODS: 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.

RESULTS: 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.

CONCLUSIONS: 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.

美国《前列腺癌》，2011年3月

在前列腺癌中转录激活蛋白p300 和 CBP可以 刺激雌激素受体- β 信号通路并调节细胞活动

简 鲍哈尔等

奥地利因斯布鲁克医科大学泌尿外科学院

背景︰ 类固醇受体激活蛋白 p300 和 CBP在晚期前列腺癌被高度表达。它们通过雄激素和抗雄性激素增强了雄激素受体的活性。在本研究中，我们提出问题，这些激活蛋白能否提高在前列腺癌中表达易变的雌激素受体 β （ER-β）的活性。

方法︰ 激活蛋白p300 和 CBP的 表达水平被细菌质粒或者 siRNA 转染操纵，并且通过荧光素酶检测方法测定ER-β 的活性。通过MTT 比色法测定了细胞生存能力并且通过细胞划痕实验和Boyden小室分析测定细胞迁移率。

结果︰当 PC3 细胞被用于实验时发现了其中ER-β的高表达。p300 或 CBP通过金雀异黄素增强 了ER-β 的活性。当任一激活蛋白的浓度被增加时雌激素没有得到有争论的性质。p300 或 CBP 的抑制降低 了金雀异黄素对ER-β 的刺激。染料木黄酮降低了前列腺癌 PC3 细胞的迁移和并且p300 的下调增强了这种效果。

结论︰在前列腺癌中p300 和 CBP 都关系到ER-β 活性的调节与细胞迁移。这些发现对理解在前列腺癌中ER-β的作用十分重要。