Fig. 5.

SRD5A1 is required for PSA expression and CRPC tumor progression in vivo. (A) Silencing SRD5A1 expression blunts PSA expression in response to AD, which is a substrate for SRD5A1, but not R1881, which does not require metabolism to bind AR. PSA expression is normalized to RPLP0 and vehicle (EtOH) control. Error bars represent the SD of experiments performed in triplicate. (B) Silencing SRD5A1 expression inhibits CRPC growth in orchiectomized mice supplemented with AD, as assessed by time for LNCaP and LAPC4 tumors to reach 50 mm³ and (C) 300 mm³. Only LAPC4 tumors reaching the 50-mm³ endpoint was statistically significantly different, although the trend for all models and time points had a disadvantage for the shSRD5A1 group. (D) Bypassing the requirement for SRD5A1 by supplementing orchiectomized mice with 5α-dione leads to nearly superimposable growth for control and shSRD5A1 LAPC4 cells. Control and shSRD5A1 groups for all xenograft studies were compared using a log rank test.