ABSTRACT
PURPOSE: recent studies have reported that the expression of Drg-1 is up-regulated by androgen. It has been suggested that Drg-1 gene be used as a molecular marker for prostate cancer therapies like PSA. To de termine the role of Drg-1 gene as a molecular marker during intermittent androgen deprivation(IAD) therapy, we investigated the expression of Drg-1 and compared it with PSA expression in human prostate cancer cell lines treated with dihydrotestosterone (DHT) continuously or intermittently. MATERIALS AND METHODS: Two prostate cancer cells having different status of androgen receptor [LNCaP (androgen dependent) and PC-3 (androgen independent)] were used in this study. To know the change in PSA and Drg-1 expression after DHT treatment the cells were cultured in steroid-free RPMI media for 24 hours. 10(-7) and 10(-8)M of DHT and 10(-7)M bicalutimide was added into the cells and then cultured for 72 hours. And we established in vitro IAD model using LNCaP cells. Northern analyses were performed to determine the expression level of both PSA and Drg-1genes. Also, western analyses were performed to determine the protein level of proliferating cellular nuclear antigen and androgen receptor. RESULTS: Transcripts of Drg-1 were detected in both LNCaP and PC-3 cells but PSA was not expressed in PC-3 cells. The expression of Drg-1gene in LNCaP cells was up-regulated by 10(-8)M of DHT like PSA gene and down-regulated by 10(-7)M bicalutamide. In the treatment of intermittent androgen deprivation, the expression pattern of Drg-1was similar to that of PSA. However, up-regulation of PSA was detected earlier than of Drg-1. CONCLUSIONS: Based on observation, Drg-1 was up-regulated by androgen and down-regulated by anti-androgen. This suggests that Drg-1gene is useful for determining the androgen independency of prostate cancer during IAD.