Androgen decreases osteoprotegerin expression in prostate cancer cells.
Osteoprotegerin (OPG), a key regulator of bone resorption, is hypothesized to have a role in prostate cancer (CaP) bone metastasis. As advanced CaP is treated by androgen ablation, we examined if androgen modulates OPG expression by CaP cell lines in vitro. Basal levels of secreted OPG protein were significantly greater in androgen-independent PC-3 cells compared with androgen-responsive LNCaP-FGC cells (P<0.001); OPG was not detected in the androgen-responsive CaP cell lines LAPC-4 or DuCaP. Treatment with 5alpha-dihydrotestosterone (5alpha-DHT) significantly decreased OPG protein levels in both PC-3 and LNCaP-FGC, with maximal suppression using 10(-9)-10(-7) M 5alpha-DHT in PC-3 (P<0.01; day 3), and using 10(-10)-10(-9) M 5alpha-DHT in LNCaP-FGC cells (P<0.01; day 6). OPG messenger RNA levels were not significantly altered by this 5alpha-DHT treatment. Co-treatment with 10(-6) M flutamide blocked 5alpha-DHT inhibition of OPG protein expression in LNCaP-FGC cells. These data suggest that androgen may modulate OPG protein levels in CaP cell lines in vitro using a post-transcriptional mechanism.
Vandyke
K
K
Oncology Research Centre, Prince of Wales Hospital, Randwick, New South Wales, Australia.
Jackson
P
P
Rowe
A
A
Russell
P J
PJ
Blair
J M
JM
D043582:5-alpha-Dihydroprogesterone / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000728:Androgens / Q000494:pharmacology*; D045744:Cell Line, Tumor; D005485:Flutamide / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D008297:Male; D053244:Osteoprotegerin / Q000096:biosynthesis*; D011471:Prostatic Neoplasms / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism
D000728:Androgens; D053244:Osteoprotegerin; D012333:RNA, Messenger; D005485:Flutamide; D043582:5-alpha-Dihydroprogesterone