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Transcriptional coactivators p300 and CBP stimulate estrogen receptor-beta signaling and regulate cellular events in prostate cancer.

AbstractBACKGROUND:
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.
AuthorsJan Bouchal, Frédéric R Santer, Philipp P S Höschele, Eva Tomastikova, Hannes Neuwirt, Zoran Culig
JournalThe Prostate (Prostate) Vol. 71 Issue 4 Pg. 431-7 (Mar 01 2011) ISSN: 1097-0045 [Electronic] United States
PMID20859991 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2010 Wiley-Liss, Inc.
Chemical References
  • Estrogen Receptor beta
  • Genistein
  • CREB-Binding Protein
  • CREBBP protein, human
  • E1A-Associated p300 Protein
  • EP300 protein, human
Topics
  • CREB-Binding Protein (physiology)
  • Cell Line, Tumor
  • Cell Movement (drug effects)
  • E1A-Associated p300 Protein (physiology)
  • Estrogen Receptor beta (genetics, physiology)
  • Genistein (pharmacology)
  • Humans
  • Male
  • Prostatic Neoplasms (pathology)
  • Signal Transduction

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