title: BIRC6 protein, an inhibitor of apoptosis: role in survival of human prostate cancer cells.
abstract: BACKGROUND
  BIRC6 is a member of the Inhibitors of Apoptosis Protein (IAP) family which is thought to protect a variety of cancer cells from apoptosis. The main objective of the present study was to investigate whether BIRC6 plays a role in prostate cancer and could be useful as a novel therapeutic target.
  
  
  METHODS
  BIRC6 expression in cell lines was assessed using Western blot analysis and in clinical samples using immunohistochemistry of tissue microarrays. The biological significance of BIRC6 was determined by siRNA-induced reduction of BIRC6 expression in LNCaP cells followed by functional assays.
  
  
  RESULTS
  Elevated BIRC6 protein expression was found in prostate cancer cell lines and clinical specimens as distinct from their benign counterparts. Increased BIRC6 expression was associated with Gleason 6-8 cancers and castration resistance. Reduction of BIRC6 expression in LNCaP cells led to a marked reduction in cell proliferation which was associated with an increase in apoptosis and a decrease in autophagosome formation. Doxorubicin-induced apoptosis was found to be coupled to a reduction in BIRC6 protein expression.
  
  
  CONCLUSIONS
  The data suggest a role for BIRC6 in prostate cancer progression and treatment resistance, and indicate for the first time that the BIRC6 gene and its product are potentially valuable targets for treatment of prostate cancers.
authors: The Vancouver Prostate Centre, Vancouver General Hospital and Department of Urologic Sciences, the University of British Columbia, Vancouver, British Columbia, Canada.
authors: Christopher G
authors: CG
authors: Low
authors: Iris S U
authors: IS
authors: Luk
authors: Dong
authors: D
authors: Lin
authors: Ladan
authors: L
authors: Fazli
authors: Kuo
authors: K
authors: Yang
authors: Yong
authors: Y
authors: Xu
authors: Martin
authors: M
authors: Gleave
authors: Peter W
authors: PW
authors: Gout
authors: Yuzhuo
authors: Y
authors: Wang
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival / Q000235:genetics; D004317:Doxorubicin / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D060787:Neoplasm Grading; D009919:Orchiectomy; D010588:Phagosomes / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000601:surgery
chemical_list: D000903:Antibiotics, Antineoplastic; C401541:BIRC6 protein, human; D051034:Inhibitor of Apoptosis Proteins; D004317:Doxorubicin