PROSTATE-SPECIFIC ANTIGEN AND ANDROGEN RECEPTOR INDUCTION AND CHARACTERIZATION OF AN IMMORTALIZED ADULT HUMAN PROSTATIC EPITHELIAL-CELL LINE

Progress in prostate cancer research has been hindered by the lack of well characterized, immortalized, human prostatic epithelial cell line s that express markers of normal prostatic epithelial cells and mimic normal growth and differentiation responses to androgens, The objectiv es of this study were to: (i) establish immortalized cell lines from n on-neoplastic, adult human prostatic epithelium using adenovirus-12/si mian virus-40 (Ad12-SV40) hybrid virus; () establish their prostatic e pithelial origin; (iii) demonstrate androgen responsiveness; and (iv) examine response to growth factors, Primary epithelial cell cultures d erived from a non-neoplastic, adult human prostate were infected with the Ad12-SV40 virus, Several immortalized clones were isolated, Single cell cloning of one clone, free of cytopathic effects, gave rise to t he PWR-1E cell line, An immortalized cell line PWR-1E, which expresses many characteristics of normal prostatic epithelial cells was establi shed, Immunostaining showed that cells express cytokeratins 8 and 18 n ormally expressed by differentiated, secretory prostatic epithelial ce lls, The most remarkable characteristics of PWR-1E cells are growth st imulation, increased expression of androgen receptor and induction of prostate specific antigen (PSA) expression in response to androgens, w hich indisputably establish their prostatic epithelial origin, They ar e positive for SV40 large-T antigen and show strong nuclear staining f or p53, Cells from passages 23 and 40 were not tumorigenic in nude mic e even when co-injected with Matrigel. They grow in a serum-free defin ed medium and respond to EGF, bFGF and TGF-P, Passage 42-cells showed a human male (XY), hyperdiploid karyotype, The PWR-1E cell line is the only known Ad12-SV40-immortalized human prostatic epithelial cell lin e, PWR-1E cells can be used to study (i) the etiology and the multiste p process of carcinogenesis and tumor progression in the human prostat e; (ii) normal prostate physiology and differentiation; and (iii) pote ntial prostate cancer chemopreventive agents.