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.
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.
Authors: M A Martinez-Balbás; A J Bannister; K Martin; P Haus-Seuffert; M Meisterernst; T Kouzarides Journal: EMBO J Date: 1998-05-15 Impact factor: 11.598
Authors: M M Zhou; B Huang; E T Olejniczak; R P Meadows; S B Shuker; M Miyazaki; T Trüb; S E Shoelson; S W Fesik Journal: Nat Struct Biol Date: 1996-04
Authors: K Shimoda; J van Deursen; M Y Sangster; S R Sarawar; R T Carson; R A Tripp; C Chu; F W Quelle; T Nosaka; D A Vignali; P C Doherty; G Grosveld; W E Paul; J N Ihle Journal: Nature Date: 1996-04-18 Impact factor: 49.962
Authors: X J Sun; L M Wang; Y Zhang; L Yenush; M G Myers; E Glasheen; W S Lane; J H Pierce; M F White Journal: Nature Date: 1995-09-14 Impact factor: 49.962
Authors: Z Culig; A Hobisch; M V Cronauer; C Radmayr; J Trapman; A Hittmair; G Bartsch; H Klocker Journal: Cancer Res Date: 1994-10-15 Impact factor: 12.701