Expression of human prostatic acid phosphatase activity and the growth of prostate carcinoma cells.
Human prostatic acid phosphatase (PAcP) is a tissue-specific differentiation antigen and is the major phosphotyrosyl (p-tyr) protein phosphatase in normal differentiated prostate epithelial cells. In prostate carcinomas, cellular PAcP has a low expression. We examined the expression of cellular PAcP activity and its correlation with cell growth that may lead us to understand the role of tyrosine phosphorylation in human prostate cells. LNCaP cells, which expressed the highest cellular PAcP activity, had the slowest growth rate and the lowest p-tyr level among three human prostate carcinoma cell lines: LNCaP, DU145, and PC-3. This inverse correlation was further examined in LNCaP cells, since these cells remain hormone-sensitive. Androgen, a classical stimulator of prostate cells, stimulated the growth of LNCaP cells while cellular PAcP activity decreased and p-tyr levels increased. This phenomenon was also observed when cells were treated with epidermal growth factor and fetal bovine serum. Both epidermal growth factor and fetal bovine serum stimulated the growth of LNCaP cells whereas cellular PAcP activity decreased. Furthermore, when cell growth was arrested at low temperatures (23 degrees C), cellular PAcP activity was elevated. To establish the relationship of cellular PAcP activity with cell growth rate, we transfected a complementary DNA encoding the full length PAcP protein into another human prostate carcinoma line, PC-3, that lacks endogenous PAcP. Two stable transfectants, designated PC-18 and PC-416 cells, were obtained and shown to express PAcP mRNA transcribed from the transfected complementary DNA. The expression of PAcP activity in PC-416 cells, but not PC-18 cells, was associated with a lower p-tyr level and a slower growth rate than control cells transfected with the expression vector alone. In conclusion, in LNCaP cells, the stimulated cell growth is associated with an increased p-tyr level and a decreased cellular PAcP activity. In PAcP complementary DNA-transfected PC-416 cells, the low level of p-tyr corresponds to a slow growth rate.
Lin
M F
MF
Department of Urology, University of Southern California School of Medicine, Los Angeles 90033.
DaVolio
J
J
Garcia-Arenas
R
R
D000135:Acid Phosphatase / Q000378:metabolism*; D001483:Base Sequence; D002277:Carcinoma / Q000201:enzymology* / Q000473:pathology; D002455:Cell Division; D004247:DNA / Q000235:genetics; D013196:Dihydrotestosterone / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D019000:Phosphotyrosine; D011471:Prostatic Neoplasms / Q000201:enzymology* / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics; D014162:Transfection; D014407:Tumor Cells, Cultured; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
D009838:Oligodeoxyribonucleotides; D012333:RNA, Messenger; D013196:Dihydrotestosterone; D019000:Phosphotyrosine; D014443:Tyrosine; D004247:DNA; D000135:Acid Phosphatase