Alteration of secretion of parathyroid hormone-related peptide and expression of its mRNA in a human hepatoma cell line (HEP G2) treated with agents that affect cell growth

Previously, using human hepatoma cells (Hep G2), we found that immunoneutralization of secreted PTHrP increased cell growth. Here we asked whether PTHrP production was affected by agents that alter growth of Hep G2 cells. Immunoreactive PTHrP in medium and PTHrP mRNA expression were examined. Treatment of cells with 10 μM hydrocortisone or 1 ng/mL TGF-β1 for 72 h inhibited cell growth by 28 ± 6 and 36 ± 2% and increased PTHrP in medium by 128 ± 10 and 525 ± 27%, respectively. The increase in PTHrP produced by both agents was dose- and time-dependent, and the increased PTHrP was accompanied by dose-and time-dependent enhanced expression of PTHrP mRNA. In contrast, 10% fetal bovine serum (FBS) for 72 h increased cell growth by 38 ± 6% (vs serum-free medium) and decreased PTHrP production by 49 ± 4% whereas culture in high glucose (3-4 g/L) increased cell growth by 43 ± 1% (vs 1 g/L glucose) and decreased PTHrP by 55 ± 0.4%. Inhibition of PTHrP by both FBS and glucose was dose-dependent; FBS also inhibited PTHrP mRNA. The results show that increased cell growth was associated with decreased PTHrP production, while decreased growth was accompanied by increased PTHrP production. The findings imply that PTHrP may help mediate growth effects of these agents on Hep G2 cells.