Recent clinical studies have raised the clinically important question of the 
relationship between dihydrotestosterone (DHT) and prostate cancer (PCa) 
progression. The significance of DHT or 5α-reductase inhibitors (5ARI) in PCa 
development and progression has not yet been fully characterized. The aim of 
this study was to determine whether the initiation of DNA replication was 
influenced by DHT in PCa. Three cell lines were used. LNCaP: a human PCa cell 
line that exhibits androgen-dependent proliferation, C4-2: a human PCa cell line 
that exhibits androgen-independent proliferation, and C4-2AT6: a castration 
resistant prostate cancer cell line. Two 5ARIs, finasteride and dutasteride, 
were used. We examined the mRNA expression of the components of pre-replication 
complex (Pre-RC), CDC6, CDT1, and MCM2-7. DHT induced cell proliferation of 
LNCaP accompanied by significantly increased CDC6, CDT1, and MCM2-7 expression. 
In contrast to LNCaP, DHT inhibited cell proliferation in C4-2AT6 cells 
accompanied by decreased expression of CDC6, CDT1, and MCM2-7. These reverse 
effects resemble the effects of 5ARIs in Pre-RC. Treatment with finasteride or 
dutasteride inhibited CDC6 expression in LNCaP, but both 5ARIs induced CDC6 
expression in C4-2 and C4-2AT6 cells.These results indicate that DHT showed 
reversal effects on PCa cell proliferation among prostate cancer cells based on 
androgen-dependence, accompanied by regulation of the initiation of DNA 
replication. 5ARIs may modulate the DNA replication system in someaggressive PCa 
through up-regulation of CDC6 expression.