title: Increased Expression of GOLPH3 is Associated with the Proliferation of Prostate Cancer.
abstract: BACKGROUND
  Golgi phosphoprotein 3 (GOLPH3) is a metastasis-associated gene, however its role in cell proliferation of prostate cancer (PCa) has not yet been elucidated.
  
  
  METHODS
  The level of expression of GOLPH3 and other genes was examined by quantitative real-time PCR (QPCR) and western blot analysis. Furthermore, we performed a comprehensive analysis of the expression of GOLPH3 in PCa using a tissue microarray (TMA) and correlated our findings with pathological parameters of PCa. RNA interference (RNAi) was used to silence the expression of GOLPH3 in PC-3 cells and to measure the effects on proliferation and cell cycle using the CCK-8 assay and flow cytometry. Western blots were also employed to assess AKT-mTOR and cell cycle-related proteins.
  
  
  RESULTS
  We showed that the expression of GOLPH3 was located at the trans-Golgi membranes in PCa cells. We found that GOLPH3 was expressed in all PCa cells and was significantly higher in two androgen-independent cell lines, DU145 and PC-3. TMA immunohistochemistry showed that GOLPH3 was positive in 64% of cancer tissue samples compared with 20% in normal and 30% in benign samples (P<0.05). In vitro, silencing GOLPH3 expression inhibited cell proliferation and arrested the cell cycle at the G2/M phase. Silencing GOLPH3 also activated P21 expression but suppressed the expression of CDK1/2 and cyclinB1 protein together with the phosphorylation of AKT and mTOR.
  
  
  CONCLUSIONS
  The expression of the GOLPH3 protein was significantly elevated in PCa. GOLPH3 can promote cell proliferation by enhancing the activity of AKT-mTOR signaling. Altogether, these findings suggest that GOLPH3 play important roles in proliferation and cell cycle regulation in PCa and might serve as promising biomarkers for PCa progression as well as potential therapeutic targets.
authors: 1. Department of Urology, Linyi People's Hospital Affiliated to Shandong University, Shandong, China ; 2. Department of Urology, Ninth People's Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.
authors: Wenzhi
authors: W
authors: Li
authors: 1. Department of Urology, Linyi People's Hospital Affiliated to Shandong University, Shandong, China.
authors: Fengfu
authors: F
authors: Guo
authors: 2. Department of Urology, Ninth People's Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.
authors: Meng
authors: M
authors: Gu
authors: 1. Department of Urology, Linyi People's Hospital Affiliated to Shandong University, Shandong, China.
authors: Guangjian
authors: G
authors: Wang
authors: 1. Department of Urology, Linyi People's Hospital Affiliated to Shandong University, Shandong, China.
authors: Xiangfei
authors: X
authors: He
authors: 2. Department of Urology, Ninth People's Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.
authors: Juan
authors: J
authors: Zhou
authors: 2. Department of Urology, Ninth People's Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.
authors: Yubing
authors: Y
authors: Peng
authors: 2. Department of Urology, Ninth People's Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.
authors: Zhong
authors: Z
authors: Wang
authors: 3. Department of Urology, HuaShan Hospital, Fudan University, Shanghai, China.
authors: Xiang
authors: X
authors: Wang
keywords: AKT; GOLPH3; cell cycle; mTOR; proliferation; prostate cancer (PCa).