RhoGDIα suppresses growth and survival of prostate cancer cells

Prostate. 2012 Mar;72(4):392-8. doi: 10.1002/pros.21441. Epub 2011 Jun 16.


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.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / metabolism*
  • Adenocarcinoma / pathology*
  • Androgens / metabolism
  • Animals
  • Apoptosis
  • Cell Line, Tumor
  • Cell Proliferation*
  • Disease Progression
  • Down-Regulation / drug effects
  • Guanine Nucleotide Dissociation Inhibitors / genetics
  • Guanine Nucleotide Dissociation Inhibitors / metabolism*
  • Humans
  • In Vitro Techniques
  • Interleukin-6 / pharmacology
  • Male
  • Mice
  • Mice, Nude
  • Prostatic Neoplasms / metabolism*
  • Prostatic Neoplasms / pathology*
  • Signal Transduction
  • Transplantation, Heterologous
  • rho Guanine Nucleotide Dissociation Inhibitor alpha
  • rho-Specific Guanine Nucleotide Dissociation Inhibitors


  • Androgens
  • Arhgdia protein, mouse
  • Guanine Nucleotide Dissociation Inhibitors
  • Interleukin-6
  • rho Guanine Nucleotide Dissociation Inhibitor alpha
  • rho-Specific Guanine Nucleotide Dissociation Inhibitors