Expression and secretion of parathyroid hormone-related protein by a human cancer cell line.

Abstract The regulation of expression of parathyroid hormone-related protein (PTHRP) mRNA by protein kinase C and cyclic-AMP-dependent pathways was studied in a human lung cancer cell line (BEN). PTHRP mRNA was increased by agents which activate protein kinase C, but not by those which activate cyclic-AMP-dependent pathways. Activators of both second messenger pathways stimulated a dose-dependent increase in the accumulation of PTHRP in conditioned medium assayed using sensitive region-specific immunoassays for PTHRP1-34 and 1-86. Calcitonin had a dose-dependent effect on the accumulation of PTHRP in culture medium which may be mediated via cyclic AMP. Varying the calcium concentration from 0–2.5 mM had no effect on peptide secretion over 20 h, while short-term incubation (30 min) with ionomycin (2.5–75 μg/ml) significantly increased PTHRP immunoreactivity in the medium.