PURPOSE: Prostate cancer frequently progresses from an initial androgen dependence to androgen independence, rendering the only effective androgen ablation therapy useless. The mechanism underlying the androgen-independent progression is incompletely understood. Interleukin (IL)-6 has been implicated in this androgen-independent progression. In this study, we tested whether IL-6 induces androgen-independent growth both in vitro and in vivo. EXPERIMENTAL DESIGN: IL-6 was expressed in androgen-sensitive LNCaP cells. The effects of IL-6 on androgen receptor activity was determined by Northern blots and gel shift assays. The effects of IL-6 on LNCaP cell growth were determined in vitro by MTT assay and in vivo. RESULTS: IL-6 can enhance the growth of androgen-sensitive LNCaP cells in the androgen-deprived condition in vitro, which is accompanied by elevation of androgen-regulated prostate-specific antigen mRNA expression. IL-6 promotes androgen-sensitive LNCaP cell tumor growth in the castrated male mice. IL-6 enhances androgen receptor DNA binding activity and nuclear translocation. The androgen-independent phenotype induced by IL-6 in LNCaP cells is accompanied by significant activation of signal transducers and activators of transcription 3 and mitogen-activated protein kinase signal pathways. CONCLUSIONS: These studies clearly provide experimental evidence that IL-6 initiates and/or enhances the transition of prostate cancer cells from an androgen-dependent to an androgen-independent phenotype.
PURPOSE:Prostate cancer frequently progresses from an initial androgen dependence to androgen independence, rendering the only effective androgen ablation therapy useless. The mechanism underlying the androgen-independent progression is incompletely understood. Interleukin (IL)-6 has been implicated in this androgen-independent progression. In this study, we tested whether IL-6 induces androgen-independent growth both in vitro and in vivo. EXPERIMENTAL DESIGN:IL-6 was expressed in androgen-sensitive LNCaP cells. The effects of IL-6 on androgen receptor activity was determined by Northern blots and gel shift assays. The effects of IL-6 on LNCaP cell growth were determined in vitro by MTT assay and in vivo. RESULTS:IL-6 can enhance the growth of androgen-sensitive LNCaP cells in the androgen-deprived condition in vitro, which is accompanied by elevation of androgen-regulated prostate-specific antigen mRNA expression. IL-6 promotes androgen-sensitive LNCaP cell tumor growth in the castrated male mice. IL-6 enhances androgen receptor DNA binding activity and nuclear translocation. The androgen-independent phenotype induced by IL-6 in LNCaP cells is accompanied by significant activation of signal transducers and activators of transcription 3 and mitogen-activated protein kinase signal pathways. CONCLUSIONS: These studies clearly provide experimental evidence that IL-6 initiates and/or enhances the transition of prostate cancer cells from an androgen-dependent to an androgen-independent phenotype.
Authors: Nagalakshmi Nadiminty; Wei Lou; Soo Ok Lee; Xin Lin; Donald L Trump; Allen C Gao Journal: Proc Natl Acad Sci U S A Date: 2006-05-01 Impact factor: 11.205
Authors: Michael Hedvat; Dennis Huszar; Andreas Herrmann; Joseph M Gozgit; Anne Schroeder; Adam Sheehy; Ralf Buettner; David Proia; Claudia M Kowolik; Hong Xin; Brian Armstrong; Geraldine Bebernitz; Shaobu Weng; Lin Wang; Minwei Ye; Kristen McEachern; Huawei Chen; Deborah Morosini; Kirsten Bell; Marat Alimzhanov; Stephanos Ioannidis; Patricia McCoon; Zhu A Cao; Hua Yu; Richard Jove; Michael Zinda Journal: Cancer Cell Date: 2009-12-08 Impact factor: 31.743