RAS ACTIVATION OF HUMAN PROSTATE EPITHELIAL-CELLS INDUCES OVEREXPRESSION OF PARATHYROID HORMONE-RELATED PEPTIDE

Immortalized adult and fetal prostate cell lines grown in serum-free c onditions produce low levels of parathyroid hormone-related peptide (P THRP) in the presence of growth factors as assessed by mRNA analysis, PTHRP immunoreactivity, and immunohistochemistry. Subsequent infection of these cells with Kirsten murine sarcoma virus containing an activa ted Ki-ms oncogene induces at least a 10-20-fold increase in PTHRP exp ression and production of both adult and fetal immortalized cell lines in the presence of the same growth factors. These results provide the first evidence of direct activation of PTHRP by the ras oncogene in h uman prostate cells and suggest its potential usefulness as a tumor ma rker in prostate malignancies.