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Relationship between Glucocorticoid Receptor Signal Pathway and Androgen-Independent Prostate Cancer

Yan T.-Z.a · Jin F.-S.b · Xie L.-P.a · Li L.-C.c
aDepartment of Urology, First Affiliated Hospital, Medical College of Zhejiang University, Hangzhou, and bDepartment of Urology, Affiliated Daping Hospital, Third Military Medical University, Chongqing, PR China; cDepartment of Urology, University of California San Francisco, and Veteran Affairs Medical Center San Francisco, San Francisco, Calif., USA Urol Int 2008;81:228–233 (DOI:10.1159/000144067)

Abstract

Objective: To study the role of the glucocorticoid receptor (GR) signal pathway and downstream cytokine interleukin-6 (IL-6) in androgen-independent growth of prostate cancer (PC). Methods: The human androgen-dependent PC (ADPC) cell line LNCaP and androgen-independent PC (AIPC) cell line DU145 were cultured in vitro. Immunocytochemistry was used to examine the expression of the androgen receptor (AR), GR, HSP90 and IL-6. The GR antagonist RU486 was used to treat cultured cells, and the effects of RU486 on the proliferation of both cell lines were analyzed by MTT assay. Expression of HSP90 and IL-6 mRNA and protein was assessed by RT-PCR and Western blots, respectively. Results: LNCaP cells were AR-positive and GR-negative, whereas DU145 cells were GR-positive and AR-negative. The expression of HSP90 and IL-6 in DU145 cells were significantly stronger than that in LNCaP cells (p < 0.01). RU486 had no obvious effects on the growth of LNCaP cells, but exerted a significant time- and dose-dependent growth inhibition on DU145 cells at doses as low as 0.1 µmol/l. RU486 treatment of DU145 cells also resulted in a dose-dependent decrease in the expression of HSP90 and IL-6 mRNA and protein. Conclusions: The GR signal pathway may be the main survival pathway for DU145 cells. Abnormal hyperactivation of the GR signal pathway and its promoting the expression of HSP90 and IL-6 contribute to the progression of ADPC to AIPC after androgen ablation.

 

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