title: RhoGDIα suppresses growth and survival of prostate cancer cells.
abstract: 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.affiliation: Department of Urology, University of California at Davis, Sacramento, California 95817, USA.
authors.forename: Yezi
authors.initials: Y
authors.lastname: Zhu
authors.forename: Ramakumar
authors.initials: R
authors.lastname: Tummala
authors.forename: Chengfei
authors.initials: C
authors.lastname: Liu
authors.forename: Nagalakshmi
authors.initials: N
authors.lastname: Nadiminty
authors.forename: Wei
authors.initials: W
authors.lastname: Lou
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Evans
authors.forename: Qinghua
authors.initials: Q
authors.lastname: Zhou
authors.forename: Allen C
authors.initials: AC
authors.lastname: Gao
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology*; D000728:Androgens / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018450:Disease Progression; D015536:Down-Regulation / Q000187:drug effects; D020730:Guanine Nucleotide Dissociation Inhibitors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D015850:Interleukin-6 / Q000494:pharmacology; D008297:Male; D051379:Mice; D008819:Mice, Nude; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology*; D015398:Signal Transduction; D014183:Transplantation, Heterologous; D062948:rho Guanine Nucleotide Dissociation Inhibitor alpha; D062947:rho-Specific Guanine Nucleotide Dissociation Inhibitors
chemical_list: D000728:Androgens; C569639:Arhgdia protein, mouse; D020730:Guanine Nucleotide Dissociation Inhibitors; D015850:Interleukin-6; D062948:rho Guanine Nucleotide Dissociation Inhibitor alpha; D062947:rho-Specific Guanine Nucleotide Dissociation Inhibitors