title: Differential phosphoprotein levels and pathway analysis identify the transition mechanism of LNCaP cells into androgen-independent cells.
abstract: BACKGROUND
  Androgen withdrawal can prolong life in men with advanced prostate cancer, but these remissions are temporary because the surviving cells progress as hormone-refractory cancer. The mechanisms that are involved in the transition of androgen-dependent prostate cancer into androgen-independent prostate cancer (AIPC) are not fully understood.
  
  
  OBJECTIVE
  To identify globally differentially expressed phosphoproteins in the androgen-independent prostate, to elucidate the molecular mechanisms that underlie the formation of AIPC and to identify new molecular targets that can be used to develop treatments for the disease.
  
  
  METHODS
  An androgen-independent LNCaP cell line, LNCaP-AI, was established using androgen ablation. Differentially expressed phosphoproteins in LNCaP cells and LNCaP-AI cells were enriched by immunoprecipitation, analyzed by 2D-PAGE and identified by MALDI-TOF MS. Total protein expression levels for two regulated proteins were confirmed by Western blot. Association network analysis was carried out using the STRING database.
  
  
  RESULTS
  The phosphorylation statuses of 17 proteins were significantly (P < 0.05) different between LNCaP-AI cells and LNCaP cells. Most proteins that were identified are known to be involved in tumor progression, and several of these proteins could be constructed into an association network. A further analysis by bioinformatics indicated that P53, HSP27, and the MAPK pathway may contribute to the transition from androgen-dependence to androgen-independence.
  
  
  CONCLUSIONS
  Blocking the MAPK signaling pathway may be useful in the treatment of AIPC.
authors: Department of Urology, Changhai Hospital, Second Military Medical University, Shanghai, China.
authors: Hui Qing
authors: HQ
authors: Wang
authors: Bo
authors: B
authors: Yang
authors: Chuan Liang
authors: CL
authors: Xu
authors: Lin Hui
authors: LH
authors: Wang
authors: Yu Xi
authors: YX
authors: Zhang
authors: Bin
authors: B
authors: Xu
authors: Jia Tao
authors: JT
authors: Ji
authors: Ying Hao
authors: YH
authors: Sun
mesh_terms: D045744:Cell Line, Tumor; D055551:HSP27 Heat-Shock Proteins / Q000502:physiology*; D006801:Humans; D015151:Immunoblotting; D020935:MAP Kinase Signaling System; D008297:Male; D010750:Phosphoproteins / Q000032:analysis*; D011471:Prostatic Neoplasms / Q000737:chemistry / Q000378:metabolism / Q000473:pathology*; D040901:Proteomics; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000502:physiology
chemical_list: D055551:HSP27 Heat-Shock Proteins; D010750:Phosphoproteins; D016159:Tumor Suppressor Protein p53; D048051:p38 Mitogen-Activated Protein Kinases