title: Transcriptional coactivators p300 and CBP stimulate estrogen receptor-beta signaling and regulate cellular events in prostate cancer.
abstract: 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.
authors.affiliation: Department of Urology, Innsbruck Medical University, Innsbruck, Austria.
authors.forename: Jan
authors.initials: J
authors.lastname: Bouchal
authors.forename: Frédéric R
authors.initials: FR
authors.lastname: Santer
authors.forename: Philipp P S
authors.initials: PP
authors.lastname: Höschele
authors.forename: Eva
authors.initials: E
authors.lastname: Tomastikova
authors.forename: Hannes
authors.initials: H
authors.lastname: Neuwirt
authors.forename: Zoran
authors.initials: Z
authors.lastname: Culig
mesh_terms: 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
chemical_list: D047629:Estrogen Receptor beta; D019833:Genistein; D050882:CREB-Binding Protein; C494363:CREBBP protein, human; D050881:E1A-Associated p300 Protein; C494360:EP300 protein, human