Transcriptional coactivators p300 and CBP stimulate estrogen receptor-beta signaling and regulate cellular events in prostate cancer.
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.
Bouchal
Jan
J
Department of Urology, Innsbruck Medical University, Innsbruck, Austria.
Santer
Frédéric R
FR
Höschele
Philipp P S
PP
Tomastikova
Eva
E
Neuwirt
Hannes
H
Culig
Zoran
Z
D050882:CREB-Binding Protein / Q000502:physiology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D050881:E1A-Associated p300 Protein / Q000502:physiology*; D047629:Estrogen Receptor beta / Q000235:genetics / Q000502:physiology*; D019833:Genistein / Q000494:pharmacology; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000473:pathology*; D015398:Signal Transduction
D047629:Estrogen Receptor beta; D019833:Genistein; D050882:CREB-Binding Protein; C494363:CREBBP protein, human; D050881:E1A-Associated p300 Protein; C494360:EP300 protein, human