Differential Expression of the Androgen-Conjugating UGT2B15 and UGT2B17 Enzymes in Prostate Tumor Cells during Cancer Progression
Pâquet S, Fazli L, Grosse L, Verreault M, Têtu B, Rennie PS, Bélanger A, Barbier O. J Clin Endocrinol Metab. 2011 Dec 14. [Epub ahead of print]


Laboratory of Molecular Pharmacology (S.P., L.G., M.V., O.B.), Centre Hospitalier Universitaire de Québec (CHUQ) Research Centre and the Faculty of Pharmacy, Laval University, Québec, Canada G1V 4G2; Department of Pathology and Laboratory of Medicine (L.F., P.S.R.), University of British Columbia, Vancouver, British Columbia, Canada V6T 1Z4; Department of Pathology (B.T.), CHUQ Research Centre, Québec, Canada G1R 2J6; and CHUQ Research Centre and the Faculty of Medicine (A.B.), Laval University, Québec, Canada G1V 0A6.


Context: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.Design:We conducted an observational study of the UGT2B15 and UGT2B17 mRNA and protein levels.Setting:The study was conducted at Laval University (Québec, Canada) and at the University of British Columbia (Vancouver, Canada).Patients/Participants: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).Main Outcome Measures: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.