5-ALPHA-REDUCTASE EXPRESSION BY PROSTATE-CANCER CELL-LINES AND BENIGNPROSTATIC HYPERPLASIA IN-VITRO

5 alpha-Reductase (5aR) activity in two human prostate cancer cell lin es was compared to that in benign prostatic hyperplasia (BPH) tissue a nd COS cells transfected with and expressing the human genes for 6 alp ha-reductase type 1 (5 alpha R1) and type 2 (5 alpha R2). Comparisons were based on pH profiles and sensitivities to selective inhibitors of 5 alpha-reductase. In the cancer lines, activity was greatest over th e pH range 7-8, compared to a sharp peak of activity between pH 5-5.5 in BPH tissue and COS cells expressing 5 alpha R2. Finasteride and SKF 105,657 were potent inhibitors of Ba-reductase activity in BPH tissue and COS cells expressing 5 alpha R2, but weak inhibitors in the cancer lines and in COS cells expressing 5 alpha R1. In contrast, UK117,026 was a more potent inhibitor of 5 alpha-reductase activity in the prost ate cancer cell lines and in COS cells expressing 5 alpha R1. These da ta indicate that human prostate cancer cell lines express 5 alpha-redu ctase activity similar to that in COS cells transfected with 5 alpha R 1, but different from that in BPH tissue. This may be a consequence of in vitro culture. Alternatively, it may reflect a change occurring as a result of neoplastic transformation, in which case it will be impor tant to select appropriate inhibitors in the clinic.