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

✍ Scribed by Grant, Ewan S.; Batchelor, Kenneth W.; Habib, Fouad K.

• Publisher: John Wiley and Sons
• Year: 1996
• Tongue: English
• Weight: 936 KB
• Volume: 29
• Category: Article
• ISSN: 0270-4137
• DOI: 10.1002/(sici)1097-0045(199612)29:6<339::aid-pros1>3.0.co;2-3

✦ Synopsis

BACKGROUND. Epithelial cells cultured from prostatic acini do not demonstrate s i g hcant (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. METHODS. 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, RTPCR analysis of total FNA using two sets of intron-spanning androgen receptor (AR) primers demonstrates the presence of full-length receptor transcripts in two BPHderived epithelial cell cultures (BPH1 and BPH2) as well as a carcinoma-derived culture (Carl). RESULTS. AR-positive LNCaP cells transfected with the AR reporter plasmid pMMTV/ SPAP exhibit sigruficant increases (P < 0.05) in SPAP production upon treatment with DHT. pW/SPAP-transfected primary epithelial cells exhibit no such response when pulsed with either androgen or anti-androgen. CONCLUSIONS. These results indicate that the lack of sighcant AR gene expression underlies the androgen independence of primary prostatic epithelial cell cultures.