Abstract

PURPOSE
Prostate specific antigen (PSA) is expressed exclusively in human prostatic epithelial cells. PSA protein has been an important biological marker for prostate cancer. Until now, very little was known about the regulation of PSA expression in prostatic cells. In this study, we were used human prostate cell lines (pRNS-1-1 and LNCaP) as in vitro model system to investigate the induction of apoptosis and the changes of expression of prostate specific antigen (PSA) in response to androgen (5 a-dihydrotestosterone: DHT) and/or 12-tetradecanoyl phorbol 13-acetate (TPA).
MATERIALS AND METHODS
DNA gel electrophoresis, flow cytometry, and microscopic analysis for the induction of apoptosis, and western blot analysis for PSA expression were used to characterize DHT and/or TPA response in human prostate cells.
RESULTS
TPA induced LNCaP Cell death. Cells exhibited morphological and ultrastructural features indication of apoptosis, cytoplasmic contraction, condensation of nuclear chromatin, and formation of membrane-bound apoptotic bodies were observed. The characteristic endonuclease- generated DNA ladder, commonly associated with apoptosis, were observed in TPA-treated and accumulation of cells in Ao (apoptotic region) LNCaP cells. But pRNS-1-1 cells showed no DNA fragmentation, no apoptotic bodies, and accumulation of cells in Ao was not observed. TPA resulted in dose-dependent inhibition of PSA expression. In contrast, DHT induced increase in PSA expression and decrease on degradation of DNA into oligonucleosomal size DNA fragment.
CONCLUSION
The data presented here suggest that DHT protects against TPA-induced apoptosis in cycling LNCaP cells and PSA expression is up-regulated predominantly by androgen, down-regulated in a dose dependent fashion by TPA.

• Keywords: Androgen;TPA;Apoptosis;PSA;Human prostate cells