EVIDENCE FOR A ROLE OF GLUCURONOSYLTRANSFERASE IN THE REGULATION OF ANDROGEN ACTION IN THE HUMAN PROSTATIC-CANCER CELL-LINE LNCAP

Citation
C. Guillemette et al., EVIDENCE FOR A ROLE OF GLUCURONOSYLTRANSFERASE IN THE REGULATION OF ANDROGEN ACTION IN THE HUMAN PROSTATIC-CANCER CELL-LINE LNCAP, Journal of steroid biochemistry and molecular biology, 57(3-4), 1996, pp. 225-231
Citations number
26
Categorie Soggetti
Biology,"Endocrynology & Metabolism
ISSN journal
09600760
Volume
57
Issue
3-4
Year of publication
1996
Pages
225 - 231
Database
ISI
SICI code
0960-0760(1996)57:3-4<225:EFAROG>2.0.ZU;2-O
Abstract
Androgens play an important role in the regulation of cell growth and specific protein synthesis in hormone-sensitive prostatic cancer. In t his study, we have investigated the metabolism of androgens in LNCaP c ells from low passage (LP) and high passage (HP) cultures which were p reviously shown to possess differential androgen responsiveness. When treated with dihydrotestosterone (DHT), cells showed the characteristi c biphasic response of cell proliferation with an ED(50) of 1 nM for b oth the LP and HP cells, but the maximal proliferative response was di fferent with values of 2.65- and 4.29-fold over basal for LP and HP ce lls, respectively. Metabolism studies indicated no difference in 5 alp ha-reductase activity between LP and HP cells, while 3 alpha-, 3 beta- and 17 beta-hydroxysteroid dehydrogenase activities were significantl y higher in LP cultures. The formation of steroid glucuronides (-G), n amely DHT-G, was higher in LP than in HP cells with values of 2.16 and 1.31 pmol of glucuronides formed/mu g DNA/3 h, respectively. Northern blot analysis with a UGT2B15 cDNA probe identified two bands correspo nding to two or more UGT transcripts in both LNCaP cells and more tran script was observed in LP than in HP cells. Taken together these resul ts indicate that DHT is deactivated more rapidly in the LP cells, whic h may explain in part the lower proliferative response to androgens of LP cells compared with HP cells. Copyright (C) 1996 Published by Else vier Science Ltd