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Androgen independence of primary epithelial cultures of the prostate is associated with a down‐regulation of androgen receptor gene expression
Author(s) -
Grant Ewan S.,
Batchelor Kenneth W.,
Habib Fouad K.
Publication year - 1996
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/(sici)1097-0045(199612)29:6<339::aid-pros1>3.0.co;2-3
Subject(s) - androgen receptor , dihydrotestosterone , androgen , lncap , biology , endocrinology , medicine , antiandrogen , transfection , cell culture , gene expression , prostate , cancer research , prostate cancer , gene , cancer , hormone , biochemistry , genetics
BACKGROUND 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. 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, 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). RESULTS 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. CONCLUSIONS These results indicate that the lack of significant AR gene expression underlies the androgen independence of primary prostatic epithelial cell cultures. © 1996 Wiley‐Liss, Inc.