Androgen independence of primary epithelial cultures of the prostate is associated with a down-regulation of androgen receptor gene expression.

Abstract

Epithelial cells cultured from prostatic acini do not demonstrate significant (P > 0.05) growth response to the testosterone metabolite dihydrotestosterone (DHT) at concentrations of 0.001-10.0 nM. In addition, the nonsteroidal antiandrogen hydroxyflutamide (HO-F) does not influence primary epithelial cell proliferation in this concentration range. Northern blotting carried out with an androgen reception (AR)-specific cDNA probe indicated that the extent of AR gene expression in six unpassaged primary prostatic epithelial cell cultures was insufficient to elicit a detectable signal upon autoradiography. However, RT/PCR analysis of total RNA using two sets of intron-spanning androgen receptor (AR) primers demonstrates the presence of full-length receptor transcripts in two BPH-derived epithelial cell cultures (BPH1 and BPH2) as well as a carcinoma-derived culture (CaP1). AR-positive LNCaP cells transfected with the AR reporter plasmid pMMTV/SPAP exhibit significant increases (P < 0.05) in SPAP production upon treatment with DHT. pMMTV/SPAP-transfected primary epithelial cells exhibit no such response when pulsed with either androgen or anti-androgen. These results indicate that the lack of significant AR gene expression underlies the androgen independence of primary prostatic epithelial cell cultures.