title: Differential expression of the androgen-conjugating UGT2B15 and UGT2B17 enzymes in prostate tumor cells during cancer progression.
abstract: BACKGROUND
  Androgens play major roles in prostate cancer initiation and development. In prostate cells, the human uridine diphosphate-glucuronosyltransferase (UGT)2B15 and UGT2B17 enzymes inactivate androgens.
  
  
  OBJECTIVE
  We investigated in vivo how UGT2B15 and UGT2B17 expressions are affected during prostate cancer development.
  
  
  METHODS
  We conducted an observational study of the UGT2B15 and UGT2B17 mRNA and protein levels.
  
  
  METHODS
  The study was conducted at Laval University (Québec, Canada) and at the University of British Columbia (Vancouver, Canada).
  
  
  METHODS
  Participants were from a cohort of prostate cancer patients from the Hôtel-Dieu de Québec hospital (Québec; mRNA analyses) and from the Vancouver Prostate Centre tissue bank (Vancouver; tissue microarray experiments).
  
  
  METHODS
  UGT mRNA and protein levels were determined using real-time PCR and immunohistochemical analyses, respectively.
  
  
  RESULTS
  Both UGT2B15 and UGT2B17 mRNA and protein levels were not significantly associated with Gleason score stratification. However, when protein levels were compared to benign prostatic hyperplasia, UGT2B17 was significantly more abundant in all Gleason-scored tumors. By contrast, UGT2B15 levels were significantly reduced in naive and castration-resistant tumors and undetectable in lymph node metastases. Finally, UGT2B17 proteins were 5-fold more abundant in metastases than in benign samples.
  
  
  CONCLUSIONS
  The current study reveals that UGT2B15 and UGT2B17 are differentially regulated during prostate cancer progression. Furthermore, this study also identifies the UGT2B15 gene as a negatively regulated target gene in castration-resistant prostate cancer and lymph node metastases.
authors.affiliation: Laboratory of Molecular Pharmacology, Centre Hospitalier Universitaire de Québec Research Centre and Faculty of Pharmacy, Laval University, 2705 Boulevard Laurier, Québec (QC), Canada G1V 4G2.
authors.forename: Sophie
authors.initials: S
authors.lastname: Pâquet
authors.forename: Ladan
authors.initials: L
authors.lastname: Fazli
authors.forename: Laurent
authors.initials: L
authors.lastname: Grosse
authors.forename: Mélanie
authors.initials: M
authors.lastname: Verreault
authors.forename: Bernard
authors.initials: B
authors.lastname: Têtu
authors.forename: Paul S
authors.initials: PS
authors.lastname: Rennie
authors.forename: Alain
authors.initials: A
authors.lastname: Bélanger
authors.forename: Olivier
authors.initials: O
authors.lastname: Barbier
mesh_terms: D018450:Disease Progression; D015972:Gene Expression Regulation, Neoplastic; D014453:Glucuronosyltransferase / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008297:Male; D015778:Minor Histocompatibility Antigens; D060787:Neoplasm Grading; D011467:Prostate / Q000201:enzymology* / Q000473:pathology; D011471:Prostatic Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology
chemical_list: D015778:Minor Histocompatibility Antigens; D014453:Glucuronosyltransferase; C472000:UDP-glucuronosyltransferase 2B15, human; C500513:UGT2B17 protein, human