HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 282, Issue 46, 33466-33474, November 16, 2007

This Article Full Text Full Text (PDF) All Versions of this Article: 282/46/33466    most recent M703370200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Chouinard, S. Articles by Bélanger, A. Search for Related Content PubMed PubMed Citation Articles by Chouinard, S. Articles by Bélanger, A. Social Bookmarking                      What's this?

UDP-glucuronosyltransferase 2B15 (UGT2B15) and UGT2B17 Enzymes Are Major Determinants of the Androgen Response in Prostate Cancer LNCaP Cells^*

Sarah Chouinard¹, Olivier Barbier^¶2, and Alain Bélanger³

From the Oncology and Molecular Endocrinology Research Center, CHUL Research Center, Québec G1V 4G2, Canada and Faculty of Medicine and ^¶Faculty of Pharmacy, Laval University, Québec G1K 7P4, Canada

Uridine diphosphate-glucuronosyltransferase 2 (UGT2)B15 and B17 enzymes conjugate dihydrotestosterone (DHT) and its metabolites androstane-3, 17-diol (3-DIOL) and androsterone (ADT). The presence of UGT2B15/B17 in the epithelial cells of the human prostate has been clearly demonstrated, and significant 3-DIOL glucuronide and ADT-glucuronide concentrations have been detected in this tissue. The human androgen-dependent cancer cell line, LNCaP, expresses UGT2B15 and -B17 and is also capable of conjugating androgens. To assess the impact of these two genes in the inactivation of androgens in LNCaP cells, their expression was inhibited using RNA interference. The efficient inhibitory effects of a UGT2B15/B17 small interfering RNA (siRNA) probe was established by the 70% reduction of these UGT mRNA levels, which was further confirmed at the protein levels. The glucuronidation of dihydrotestosterone (DHT), 3-DIOL, and ADT by LNCaP cell homogenates was reduced by more than 75% in UGT2B15/B17 siRNA-transfected LNCaP cells when compared with cells transfected with a non-target probe. In UGT2B15/B17-deficient LNCaP cells, we observe a stronger response to DHT than in control cells, as determined by cell proliferation and expression of eight known androgen-sensitive genes. As expected, the amounts of DHT in cell culture media from control cells were significantly lower than that from UGT2B15/B17 siRNA-treated cells, which was caused by a higher conversion to its corresponding glucuronide derivative. Taken together these data support the idea that UGT2B15 and -B17 are critical enzymes for the local inactivation of androgens and that glucuronidation is a major determinant of androgen action in prostate cells.

Received for publication, April 23, 2007 , and in revised form, August 14, 2007.

^* This work was supported in part by Canadian Institutes of Health Research Grant MOP-64273 and the Fonds de la Recherche en Santé du Québec. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ Holds a scholarship from the Canadian Institutes of Health Research.

² Recipient of a grant by the Health Research Foundation of Rx&D-Canadian Institutes of Health Research.

³ To whom correspondence should be addressed: Oncology and Molecular Endocrinology Research Center, CHUL Research Center, 2705 Laurier Blvd. Bloc T-3, Québec G1V 4G2, Canada. Tel.: 418-654-2296; Fax: 418-654-2761; E-mail: alain.belanger{at}ap.ulaval.ca.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				R. H. Takahashi, T. A. Grigliatti, R. E. Reid, and K. W. Riggs The Effect of Allelic Variation in Aldo-Keto Reductase 1C2 on the in Vitro Metabolism of Dihydrotestosterone J. Pharmacol. Exp. Ther., June 1, 2009; 329(3): 1032 - 1039. [Abstract] [Full Text] [PDF]

				Q. Wei, R. Galbenus, A. Raza, R. L. Cerny, and M. A. Simpson Androgen-Stimulated UDP-Glucose Dehydrogenase Expression Limits Prostate Androgen Availability without Impacting Hyaluronan Levels Cancer Res., March 15, 2009; 69(6): 2332 - 2339. [Abstract] [Full Text] [PDF]

				J. Kaeding, J. Belanger, P. Caron, M. Verreault, A. Belanger, and O. Barbier Calcitrol (1{alpha},25-dihydroxyvitamin D3) inhibits androgen glucuronidation in prostate cancer cells Mol. Cancer Ther., February 1, 2008; 7(2): 380 - 390. [Abstract] [Full Text] [PDF]