Overexpression of 5α-reductase type 1 increases sensitivity of prostate cancer cells to low concentrations of testosterone

• Published in: The Prostate 2009-05, Vol.69 (6), p.595-602
• Main Authors: Thomas, Lynn N., Douglas, Robert C., Rittmaster, Roger S., Too, Catherine K.L.
• Format: Article
• Language: English
• Subjects: 3-Oxo-5-alpha-Steroid 4-Dehydrogenase - genetics; castration-recurrent prostate cancer; Cell Line, Tumor; dihydrotestosterone; DNA Primers; DNA, Complementary - genetics; DNA, Complementary - isolation & purification; DNA, Neoplasm - genetics; DNA, Neoplasm - isolation & purification; dutasteride; finasteride; Gene Expression Regulation, Enzymologic; Gene Expression Regulation, Neoplastic; Humans; Isoenzymes - genetics; Male; Prostate-Specific Antigen - genetics; Prostatic Neoplasms - enzymology; Prostatic Neoplasms - genetics; Prostatic Neoplasms - pathology; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - genetics; RNA, Neoplasm - genetics; Testosterone - pharmacology; Transfection; Up-Regulation
• ISSN: 0270-4137; 1097-0045
• DOI: 10.1002/pros.20911

INTRODUCTION Conversion of testosterone to dihydrotestosterone (DHT) by the enzymes 5α‐reductase types 1 (5αR1) and 2 (5αR2) is important for normal and pathological growth of the prostate. The predominant isoenzyme in normal prostate is 5αR2. However, prostate cancer (PCa) development is accompanied by a decrease in 5αR2 and an increase in 5αR1. The biological significance of increased 5αR1 expression is not fully understood. Therefore, the aim of this study was to determine the effect of overexpression of 5αR1 on growth and prostate‐specific antigen (PSA) production in PCa cells. MATERIALS AND METHODS LNGK‐9 PCa cells, transiently transfected with pTRE‐5αR1 or pTRE alone, were cultured in the presence or absence of testosterone at varying concentrations. Cell growth and PSA secretion were measured after 4–6 days. Cyclin E1, Ki67, and PSA mRNA levels were evaluated using RT‐PCR after 24 hr of treatment. RESULTS 10 pM testosterone increased growth of pTRE‐5αR1 transfectants by 54.1% over cells grown in the absence of testosterone, compared to 25.0% in pTRE transfectants (P