BACKGROUND: Accumulating evidence suggest a critical role of activation of androgen receptor (AR) by nonandrogen in the development of androgen independent prostate cancer. Previous study identified that interleukin-4 (IL-4) enhances AR activation in the absence of androgen or in the very low levels of androgen in prostate cancer cells. In this study, the mechanism of IL-4-induced AR activation was investigated. METHODS & RESULTS: The induction of AR activation by IL-4 can be suppressed by expression of the I(kappa)B(alpha), an inhibitor of NF-(kappa)B. The enhanced expression of AR-mediated prostate-specific antigen (PSA) by IL-4 was blocked by the expression of I(kappa)B(alpha). IL-4 increases NF-(kappa)B transcriptional activity in prostate cancer cells which can be blocked by the addition of IL-4 antibody. IL-4 can also rapidly activate NF-kappaB. Furthermore, the IL-4-induced NF-kappaB activation and nuclear translocation can be blocked by LY294002, a PI3K/Akt specific inhibitor, suggesting that IL-4-induced NF-(kappa)B activation is mediated by activation of PI3K/Akt pathway. CONCLUSION: In combination with previous study that IL-4 activates PI3K/Akt pathway, activation of PI3K/Akt > NF-(kappa)B pathways may be responsible for IL-4-induced AR activation in prostate cancer cells. Taken together, these studies suggest that IL-4 > PI3K/Akt > NF-(kappa)B signaling pathways, which activate AR signaling, may play an important role during the progression of androgen independent prostate cancer cells. (c) 2005 Wiley-Liss, Inc.
BACKGROUND: Accumulating evidence suggest a critical role of activation of androgen receptor (AR) by nonandrogen in the development of androgen independent prostate cancer. Previous study identified that interleukin-4 (IL-4) enhances AR activation in the absence of androgen or in the very low levels of androgen in prostate cancer cells. In this study, the mechanism of IL-4-induced AR activation was investigated. METHODS & RESULTS: The induction of AR activation by IL-4 can be suppressed by expression of the I(kappa)B(alpha), an inhibitor of NF-(kappa)B. The enhanced expression of AR-mediated prostate-specific antigen (PSA) by IL-4 was blocked by the expression of I(kappa)B(alpha). IL-4 increases NF-(kappa)B transcriptional activity in prostate cancer cells which can be blocked by the addition of IL-4 antibody. IL-4 can also rapidly activate NF-kappaB. Furthermore, the IL-4-induced NF-kappaB activation and nuclear translocation can be blocked by LY294002, a PI3K/Akt specific inhibitor, suggesting that IL-4-induced NF-(kappa)B activation is mediated by activation of PI3K/Akt pathway. CONCLUSION: In combination with previous study that IL-4 activates PI3K/Akt pathway, activation of PI3K/Akt > NF-(kappa)B pathways may be responsible for IL-4-induced AR activation in prostate cancer cells. Taken together, these studies suggest that IL-4 > PI3K/Akt > NF-(kappa)B signaling pathways, which activate AR signaling, may play an important role during the progression of androgen independent prostate cancer cells. (c) 2005 Wiley-Liss, Inc.
Authors: Diping Wang; R Bruce Montgomery; Lucy J Schmidt; Elahe A Mostaghel; Haojie Huang; Peter S Nelson; Donald J Tindall Journal: Cancer Res Date: 2009-12-15 Impact factor: 12.701
Authors: Thomas Nelius; Stephanie Filleur; Alexander Yemelyanov; Irina Budunova; E Shroff; Yelena Mirochnik; Arin Aurora; Dorina Veliceasa; Wuhan Xiao; Zhou Wang; Olga V Volpert Journal: Int J Cancer Date: 2007-09-01 Impact factor: 7.396