5 alpha-reductase expression by prostate cancer cell lines and benign prostatic hyperplasia in vitro.
5 alpha-reductase (5 alpha R) activity in two human prostate cancer cell lines was compared to that in benign prostatic hyperplasia (BPH) tissue and COS cells transfected with and expressing the human genes for 5 alpha-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 the 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 SKF105,657 were potent inhibitors of 5 alpha-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 prostate cancer cell lines and in COS cells expressing 5 alpha R1. These data indicate that human prostate cancer cell lines express 5 alpha-reductase activity similar to that in COS cells transfected with 5 alpha R1, 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 important to select appropriate inhibitors in the clinic.
Smith
C M
CM
University College London, Institute of Urology and Nephrology, Research Laboratories, United Kingdom.
Ballard
S A
SA
Worman
N
N
Buettner
R
R
Masters
J R
JR
D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000096:biosynthesis* / Q000378:metabolism; D000818:Animals; D001483:Base Sequence; D001932:Brain Neoplasms / Q000201:enzymology / Q000556:secondary; D002460:Cell Line; D002522:Chlorocebus aethiops; D017931:DNA Primers; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015870:Gene Expression; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007527:Isoenzymes / Q000096:biosynthesis / Q000378:metabolism; D007700:Kinetics; D008297:Male; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011470:Prostatic Hyperplasia / Q000201:enzymology*; D011471:Prostatic Neoplasms / Q000201:enzymology*; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000378:metabolism; D014162:Transfection; D014407:Tumor Cells, Cultured
D017931:DNA Primers; D004791:Enzyme Inhibitors; D007527:Isoenzymes; D011994:Recombinant Proteins; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase