Prostate androgen-regulated gene: a novel potential target for androgen-independent prostate cancer therapy.

AIM

To investigate the involvement of the prostate androgen-regulated (PAR) gene in the androgen receptor (AR) signaling pathway and the malignant phenotype of androgen-independent prostate cancer (PCa) cells.

METHODS

The difference in PAR expression between LNCaP and PC3 cells was detected by reverse transcription-polymerase chain reaction (RT-PCR). Androgen and anti-androgen effects on PAR expression were evaluated by RT-PCR in LNCaP, PC3 cells and PC3 cells stably transfected with vector containing wild-type AR. To determine the importance of PAR in the malignant proliferation of androgen-independent PCa cells, we used small interfering RNA (siRNA) transfection to knock down the expression of the gene in PC3 cells. The changes in the malignant phenotype of PCa cells after transfection were analyzed by cell count, colony formation in soft agar and flow cytometry.

RESULTS

PAR expression was 3-fold higher in PC3 cells than that in LNCaP cells. Dihydrotestosterone (DHT) regulated PAR mRNA expression in LNCaP cells and the effect was inhibited by the AR antagonist, flutamide. By contrast, DHT did not affect PAR expression in PC3 cells. The reintroduction of AR into PC3 cells by stable transfection restored the androgen effect on PAR upregulation. After the knockdown of the PAR gene by siRNA, PC3 cells exhibited a reversal of the malignant phenotype.

CONCLUSION

Because of the possibility that PAR is downstream from the AR, and because of its contribution to malignant proliferation in androgen-independent PCa cells, the gene could be a potential therapeutic target for androgen-independent PCa with AR signaling pathway alteration.