BACKGROUND: Treatment for primary prostate cancer (CaP) is the withdrawal of androgens. However, CaP eventually progresses to grow in a castration-resistant state. The mechanisms involved in the development and progression of castration-resistant prostate cancer (CRPC) remain unknown. We have previously generated LNCaP-IL6+ cells by treating LNCaP cells chronically with interleukin-6 (IL-6), which have acquired the ability to grow in androgen-deprived conditions. METHODS: We compared the protein expression profile of LNCaP and LNCaP-IL6+ cells using two-dimensional gel electrophoresis. The gels were then silver stained in order to visualize proteins and the differentially expressed spots were identified and characterized by micro sequencing using MALDI-PMF mass spectrometry. RESULTS: In this study, we have identified RhoGDIα (GDIα) as a suppressor of CaP growth. Expression of GDIα was reduced in LNCaP-IL6+ cells and was down-regulated in more aggressive CaP cells compared to LNCaP cells. Over expression of GDIα inhibited the growth of CaP cells and caused LNCaP-IL6+ cells reversal to androgen-sensitive state, while down-regulation of GDIα enhanced growth of androgen-sensitive LNCaP CaP cells in androgen-deprived conditions. In addition, GDIα suppressed the tumorigenic ability of prostate tumor xenografts in vivo. CONCLUSIONS: These results demonstrate that loss of GDIα expression promotes the development and progression of prostate cancer.
BACKGROUND: Treatment for primary prostate cancer (CaP) is the withdrawal of androgens. However, CaP eventually progresses to grow in a castration-resistant state. The mechanisms involved in the development and progression of castration-resistant prostate cancer (CRPC) remain unknown. We have previously generated LNCaP-IL6+ cells by treating LNCaP cells chronically with interleukin-6 (IL-6), which have acquired the ability to grow in androgen-deprived conditions. METHODS: We compared the protein expression profile of LNCaP and LNCaP-IL6+ cells using two-dimensional gel electrophoresis. The gels were then silver stained in order to visualize proteins and the differentially expressed spots were identified and characterized by micro sequencing using MALDI-PMF mass spectrometry. RESULTS: In this study, we have identified RhoGDIα (GDIα) as a suppressor of CaP growth. Expression of GDIα was reduced in LNCaP-IL6+ cells and was down-regulated in more aggressive CaP cells compared to LNCaP cells. Over expression of GDIα inhibited the growth of CaP cells and caused LNCaP-IL6+ cells reversal to androgen-sensitive state, while down-regulation of GDIα enhanced growth of androgen-sensitive LNCaP CaP cells in androgen-deprived conditions. In addition, GDIα suppressed the tumorigenic ability of prostate tumor xenografts in vivo. CONCLUSIONS: These results demonstrate that loss of GDIα expression promotes the development and progression of prostate cancer.
Authors: Ines Barone; Lauren Brusco; Guowei Gu; Jennifer Selever; Amanda Beyer; Kyle R Covington; Anna Tsimelzon; Tao Wang; Susan G Hilsenbeck; Gary C Chamness; Sebastiano Andò; Suzanne A W Fuqua Journal: J Natl Cancer Inst Date: 2011-03-29 Impact factor: 13.506