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

Sammanfattning

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.

Nyckelord

transcriptional coactivators; prostate cancer; estrogen receptor-beta; migration; genistein

Publicerad i

Prostate
2011, Volym: 71, nummer: 4, sidor: 431-437
Utgivare: WILEY-BLACKWELL

UKÄ forskningsämne

Urologi och njurmedicin


Publikationens identifierare

DOI: https://doi.org/10.1002/pros.21257

Permanent länk till denna sida (URI)

https://res.slu.se/id/publ/85597