Regulation of prostate-specific antigen gene expression by an LH-RH analogue in human prostatic cells.
BACKGROUND
We investigated the regulation of prostate-specific antigen (PSA) gene expression in prostatic tumor cells by an LH-RH analogue, Leuprorelin acetate (LH-RHa), alone or combined with dihydrotestosterone (DHT).


METHODS
PSA gene expression was evaluated by Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR) in androgen-sensitive LNCaP and androgen-insensitive PC-3 cells.


RESULTS
LH-RHa at both high and low concentrations induced a diminution in the levels of PSA gene expression which reached 70% in androgen-insensitive PC-3 cells. The analogue lowered the levels of expression obtained under DHT stimulation in LNCaP cells. These effects were visible from 6-24 hours of treatment and persisted until 120 hours.


CONCLUSIONS
PSA gene expression is directly regulated by LH-RHa in both LNCaP and PC-3 cells. High concentrations of the analogue are particularly effective, but low doses of the drug have a similar behaviour. Interestingly, Leuprorelin acetate is able to counteract the androgen-induced gene expression. Our results suggest that, at least in androgen-sensitive cells, the analogue may regulate PSA gene expression also by interfering with the androgen receptor machinery.
Sica
Gigliola
G
Istituto di Istologia ed Embriologia, Facoltà di Medicina e Chirurgia, Università Cattolica del Sacro Cuore, Largo F. Vito n. 1, 00168 Roma, Italia. ibiis@rm.unicatt.it
Zelano
Giovanni
G
Settesoldi
Daniela
D
Iacopino
Fortunata
F
D000230:Adenocarcinoma / Q000473:pathology*; D000728:Androgens; D000951:Antigens, Neoplasm / Q000096:biosynthesis* / Q000235:genetics; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology*; D013196:Dihydrotestosterone / Q000037:antagonists & inhibitors; D004305:Dose-Response Relationship, Drug; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D016729:Leuprolide / Q000494:pharmacology*; D008297:Male; D009376:Neoplasms, Hormone-Dependent / Q000473:pathology*; D017430:Prostate-Specific Antigen / Q000096:biosynthesis* / Q000235:genetics; D011471:Prostatic Neoplasms / Q000473:pathology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism
D000728:Androgens; D000951:Antigens, Neoplasm; D018931:Antineoplastic Agents, Hormonal; D013196:Dihydrotestosterone; D017430:Prostate-Specific Antigen; D016729:Leuprolide