title: BCAS2 promotes prostate cancer cells proliferation by enhancing AR mRNA transcription and protein stability.
abstract: BACKGROUND
  We showed previously that breast carcinoma amplified sequence 2 (BCAS2) functions as a negative regulator of p53. We also found that BCAS2 is a potential AR-associated protein. AR is essential for the growth and survival of prostate carcinoma. Therefore we characterised the correlation between BCAS2 and AR.
  
  
  METHODS
  Protein interactions were examined by GST pull-down assay and co-immunoprecipitation. Clinical prostate cancer (PCa) specimens were evaluated by immunohistochemical assay. AR transcriptional activity and LNCaP cell growth were assessed by luciferase assay and MTT assay, respectively.
  
  
  RESULTS
  BCAS2 expression was significantly increased in PCa. BCAS2 stabilised AR protein through both hormone-dependent and -independent manners. There are at least two mechanisms for BCAS2-mediated AR protein upregulation: One is p53-dependent. The p53 is suppressed by BCAS2 that results in increasing AR mRNA and protein expression. The other is via p53-independent inhibition of proteasome degradation. As BCAS2 can form a complex with AR and HSP90, it may function with HSP90 to stabilise AR protein from being degraded by proteasome.
  
  
  CONCLUSIONS
  In this study, we show that BCAS2 is a novel AR-interacting protein and characterise the correlation between BCAS2 and PCa. Thus we propose that BCAS2 could be a diagnostic marker and therapeutic target for PCa.
authors.affiliation: Graduate Institute of Microbiology, College of Medicine, National Taiwan University, Taipei 100, Taiwan.
authors.forename: P-C
authors.initials: PC
authors.lastname: Kuo
authors.affiliation: Graduate Institute of Microbiology, College of Medicine, National Taiwan University, Taipei 100, Taiwan.
authors.forename: C-W
authors.initials: CW
authors.lastname: Huang
authors.affiliation: Graduate Institute of Microbiology, College of Medicine, National Taiwan University, Taipei 100, Taiwan.
authors.forename: C-I
authors.initials: CI
authors.lastname: Lee
authors.affiliation: Graduate Institute of Microbiology, College of Medicine, National Taiwan University, Taipei 100, Taiwan.
authors.forename: H-W
authors.initials: HW
authors.lastname: Chang
authors.affiliation: Taipei Hospital, Ministry of Health and Welfare, New Taipei City 242, Taiwan.
authors.forename: S-W
authors.initials: SW
authors.lastname: Hsieh
authors.affiliation: Taipei Hospital, Ministry of Health and Welfare, New Taipei City 242, Taiwan.
authors.forename: Y-P
authors.initials: YP
authors.lastname: Chung
authors.affiliation: Graduate Institute of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, Taipei 100, Taiwan.
authors.forename: M-S
authors.initials: MS
authors.lastname: Lee
authors.affiliation: Department of Surgery, National Taiwan University Hospital, Taipei 100, Taiwani.
authors.forename: C-S
authors.initials: CS
authors.lastname: Huang
authors.affiliation: Graduate Institute of Microbiology, College of Medicine, National Taiwan University, Taipei 100, Taiwan.
authors.forename: L-P
authors.initials: LP
authors.lastname: Tsao
authors.affiliation: Department of Ophthalmology, Mackay Memorial Hospital, Taipei 104, Taiwan.
authors.forename: Y-P
authors.initials: YP
authors.lastname: Tsao
authors.affiliation: Graduate Institute of Microbiology, College of Medicine, National Taiwan University, Taipei 100, Taiwan.
authors.forename: S-L
authors.initials: SL
authors.lastname: Chen
mesh_terms: D016227:Benzoquinones / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015972:Gene Expression Regulation, Neoplastic; D057809:HEK293 Cells; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors; D006207:Half-Life; D006801:Humans; D020128:Inhibitory Concentration 50; D047029:Lactams, Macrocyclic / Q000494:pharmacology; D008297:Male; D060787:Neoplasm Grading; D009363:Neoplasm Proteins / Q000502:physiology*; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D055550:Protein Stability; D059748:Proteolysis; D011944:Receptors, Androgen / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: C120624:BCAS2 protein, human; D016227:Benzoquinones; D018841:HSP90 Heat-Shock Proteins; D047029:Lactams, Macrocyclic; D009363:Neoplasm Proteins; D011944:Receptors, Androgen; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C112765:tanespimycin; D046988:Proteasome Endopeptidase Complex