title: Interleukin-4 activates androgen receptor through CBP/p300.
abstract: BACKGROUND
  Aberrant activation of androgen receptor (AR) plays an important role in the progression of castration resistant prostate cancer. Interleukin-4 (IL-4) enhances AR activation in the absence of androgen and stimulates castration resistant growth of androgen-sensitive prostate cancer cells. However, the mechanism of IL-4 mediated AR activation has not yet been revealed.
  
  
  METHODS
  The effect of IL-4 on CBP/p300 expression was examined by Western blot analysis. The effect of IL-4 on the interactions of AR and CBP/p300 was examined by co-immunoprecipitation and ChIP assays. CBP/p300 siRNA was used to knockdown CBP/p300 expression to examine the role of CBP/p300 expression on IL-4 mediated AR activation.
  
  
  RESULTS
  We found that IL-4 increases CBP/p300 protein expression and enhances interaction of AR with CBP/p300 proteins through an increase in the recruitment of CBP/p300 protein to the androgen responsive elements in the promoters of androgen responsive genes. Down regulation of CBP/p300 expression using CBP/p300 specific siRNA abolished IL-4 mediated AR activation, suggesting that CBP/p300 is responsible for AR activation induced by IL-4. Furthermore, AR activation can be enhanced by AR acetylation induced by IL-4 in prostate cancer cells. The IL-4 mediated AR acetylation can be blocked by knocking down CBP/p300 expression using CBP/p300 specific siRNA.
  
  
  CONCLUSIONS
  These results suggest that IL-4 activates AR through enhanced expression of CBP/p300 and its histone acetyltransferase activity.
authors.affiliation: Department of Urology and Cancer Center, University of California Davis Medical Center, Sacramento, California 95817, USA.
authors.forename: Soo Ok
authors.initials: SO
authors.lastname: Lee
authors.forename: Jae Yeon
authors.initials: JY
authors.lastname: Chun
authors.forename: Nagalakshmi
authors.initials: N
authors.lastname: Nadiminty
authors.forename: Wei
authors.initials: W
authors.lastname: Lou
authors.forename: Siting
authors.initials: S
authors.lastname: Feng
authors.forename: Allen C
authors.initials: AC
authors.lastname: Gao
mesh_terms: D001665:Binding Sites; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000187:drug effects / Q000502:physiology*; D016384:Consensus Sequence; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D051548:Histone Acetyltransferases / Q000235:genetics; D006801:Humans; D015847:Interleukin-4 / Q000494:pharmacology*; D008297:Male; D011471:Prostatic Neoplasms; D011944:Receptors, Androgen / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D050880:p300-CBP Transcription Factors / Q000502:physiology*
chemical_list: D011944:Receptors, Androgen; D015847:Interleukin-4; D051548:Histone Acetyltransferases; D050880:p300-CBP Transcription Factors