Transcriptional Coactivators p300 and CBP Stimulate Estrogen Receptor-Beta Signaling and Regulate Cellular Events in Prostate Cancer
Transcriptional Coactivators p300 and CBP Stimulate Estrogen Receptor-Beta Signaling and Regulate Cellular Events in Prostate Cancer
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DOI：
10.1002/pros.21257
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发表时间：
2011-03-01
期刊：
影响因子：
2.8
通讯作者：
Culig, Zoran
中科院分区：
文献类型：
--
作者：
Bouchal, Jan;Santer, Frederic R.;Culig, Zoran
背景资料。类固醇受体辅活化子p300和CBP在晚期前列腺癌中高表达。它们通过雄激素和抗雄激素来增强雄激素受体的激活。在目前的研究中，我们已经解决了这些共激活剂是否增强雌激素受体-β(ER-β)活性的问题，雌激素受体-β在前列腺癌中有不同的表达。方法：研究方法。共激活子p300和CBP的表达水平通过质粒或siRNA的转染法进行调控，并通过荧光素酶检测ER-β的活性。用四甲基偶氮唑盐比色法测定细胞活力，用伤口愈合试验和Boyden小室试验测定细胞迁移能力。结果。在用于实验的PC3细胞中发现ER-β的高表达。P300或CBP增强染料木素对ER-β的激活作用。在任何一种辅助激活剂浓度增加的情况下，抗雌激素并不具有激动性。抑制p300或CBP可降低金雀异黄素对ER-β的刺激。金雀异黄素减少了PC3前列腺癌细胞的迁移，而p300的下调加强了这一作用。结论。P300和CBP参与了前列腺癌ER-β活性和细胞迁移的调节。这些发现对于了解ER-β在前列腺癌中的作用很重要。前列腺癌71：431-437,2011。(C)2010年Wiley-Liss公司
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-beta), 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-beta 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-beta was found in PC3 cells which were used for the experiments. p300 or CBP enhanced activation of ER-beta 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-beta. 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-beta activity and cellular migration in prostate cancer. These findings are important for understanding of action of ER-beta in carcinoma of the prostate. Prostate 71: 431-437, 2011. (C) 2010 Wiley-Liss, Inc.