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).

MATERIALS AND 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.

CONCLUSION

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.