Regulation of the expression of prostatic acid phosphatase in LNCaP human prostate carcinoma cells.
Human prostatic acid phosphatase (PAcP) is a prostate epithelium-specific differentiation antigen and its expression has been proposed to be regulated by androgens. Since cellular PAcP may function as a protein tyrosine phosphatase, we investigated the regulatory mechanism of its expression at different growth stages in LNCaP cells, the only cultured human prostate carcinoma cells that express an endogenous PAcP. Cells were plated at different densities to represent different stages of cellular growth for quantitating the expression of PAcP. In 4-d subconfluent cells, the cellular PAcP activity and protein level increased following the seeded cell density, consistent with mRNA levels. By day 7, all cultures had an approximately equal amount of total cellular proteins, indicating that cell growth approached to confluence, except the one that was plated at the lowest density. The cellular PAcP activity per cell was increased and corresponded to its protein level as observed in 4-d cultures. However, in 7-d cultured cells, although the PAcP protein level increased, its mRNA level declined. This increased PAcP protein level despite the decreased message was in part due to a prolonged half-life of the protein. Further, androgen effect on the PAcP mRNA level was also shown to be a cell density-dependent phenomenon. In low-density cultured cells, the PAcP mRNA level was elevated approximately 100% by 5 alpha-dihydrotestosterone (DHT) stimulation. However, in high-density confluent cells the mRNA level was slightly decreased by DHT treatment. Further, treatments with various growth stimulators resulted in various degrees of inhibition on PAcP mRNA levels. In conclusion, the data indicate that the cellular level of PAcP activity is associated with the cell density/confluence of LNCaP cells. Further, cell density could modulate androgen effect on PAcP expression at the mRNA level.
Lin
M F
MF
Department of Urology, University of Southern California School of Medicine, Los Angeles 90033.
Garcia-Arenas
R
R
Kawachi
M
M
Lin
F F
FF
D000135:Acid Phosphatase / Q000235:genetics* / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000235:genetics; D002452:Cell Count; D002455:Cell Division; D013196:Dihydrotestosterone / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006207:Half-Life; D006801:Humans; D008297:Male; D011467:Prostate / Q000201:enzymology*; D011471:Prostatic Neoplasms / Q000201:enzymology* / Q000235:genetics* / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000201:enzymology / Q000473:pathology
D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D013196:Dihydrotestosterone; D000135:Acid Phosphatase