Interleukin-4 activates androgen receptor through CBP/p300

Soo Ok Lee, Jae Yeon Chun, Nagalakshmi Nadiminty, Wei Lou, Siting Feng, Allen C Gao

Research output: Contribution to journalArticle

25 Scopus citations

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. CONCLUSION. These results suggest that IL-4 activates AR through enhanced expression of CBP/p300 and its histone acetyltransferase activity.

Original languageEnglish (US)
Pages (from-to)126-132
Number of pages7
JournalProstate
Volume69
Issue number2
DOIs
StatePublished - Feb 1 2009

Keywords

  • AR
  • CBP/p300
  • Interleukin-4
  • Prostate cancer

ASJC Scopus subject areas

  • Urology
  • Oncology
  • Medicine(all)

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    Lee, S. O., Chun, J. Y., Nadiminty, N., Lou, W., Feng, S., & Gao, A. C. (2009). Interleukin-4 activates androgen receptor through CBP/p300. Prostate, 69(2), 126-132. https://doi.org/10.1002/pros.20865