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 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.
Grant
E S
ES
Department of Surgery/Urology, University of Edinburgh, U.K.
Batchelor
K W
KW
Habib
F K
FK
D000726:Androgen Antagonists / Q000494:pharmacology; D000728:Androgens / Q000494:pharmacology* / Q000502:physiology; D001483:Base Sequence; D015152:Blotting, Northern; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D004273:DNA, Neoplasm / Q000032:analysis / Q000737:chemistry / Q000235:genetics; D013196:Dihydrotestosterone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects* / Q000502:physiology; D004848:Epithelium / Q000737:chemistry / Q000187:drug effects / Q000473:pathology; D005485:Flutamide / Q000031:analogs & derivatives / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011471:Prostatic Neoplasms / Q000737:chemistry / Q000473:pathology* / Q000503:physiopathology; D012333:RNA, Messenger / Q000032:analysis / Q000737:chemistry / Q000235:genetics; D011944:Receptors, Androgen / Q000032:analysis / Q000235:genetics* / Q000502:physiology; D014162:Transfection; D014407:Tumor Cells, Cultured
D000726:Androgen Antagonists; D000728:Androgens; D004273:DNA, Neoplasm; D012333:RNA, Messenger; D011944:Receptors, Androgen; D013196:Dihydrotestosterone; C014290:hydroxyflutamide; D005485:Flutamide