ANDROGEN INDEPENDENCE OF PRIMARY EPITHELIAL CULTURES OF THE PROSTATE IS ASSOCIATED WITH A DOWN-REGULATION OF ANDROGEN RECEPTOR GENE-EXPRESSION

BACKGROUND. Epithelial cells cultured from prostatic acini do not demo nstrate significant (P > 0.05) growth response to the testosterone met abolite dihydrotestosterone (DHT) at concentrations of 0.001-10.0 nM. In addition, the nonsteroidal antiandrogen hydroxyflutamide (HO-F) doe s not influence primary epithelial cell proliferation in this concentr ation range. METHODS. Northern blotting carried out with an androgen r eception (AR)-specific cDNA probe indicated that the extent of AR gene expression in six unpassaged primary prostatic epithelial cell cultur es was insufficient to elicit a detectable signal upon autoradiography . However, RT/PCR analysis of total RNA using two sets of intron-spann ing androgen receptor (AR) primers demonstrates the presence of full-l ength receptor transcripts in two BPH-derived epithelial cell cultures (BPH1 and BPH2) as well as a carcinoma-derived culture (CaP1). RESULT S. AR-positive LNCaP cells transfected with the AR reporter plasmid pM MTV/SPAP exhibit significant increases (P < 0.05) in SPAP production u pon treatment with DHT. pMMTV/SPAP-transfected primary epithelial cell s exhibit no such response when pulsed with either androgen or anti-an drogen. CONCLUSIONS. These results indicate that the lack of significa nt AR gene expression underlies the androgen independence of primary p rostatic epithelial cell cultures. (C) 1996 Wiley-Liss, Inc.