CYCLIC-AMP INCREASES THE RELEASE OF PARATHYROID HORMONE-RELATED PROTEIN FROM A LUNG-CANCER CELL-LINE

Parathyroid hormone-related protein (PTHrP) plays an important role in the pathogenesis of malignant hypercalcemia by stimulating bone resor ption and/or renal tubular reabsorption of calcium. In cultured cancer cells, its production can be influenced by various factors or ions, b ut the regulation of its production is still poorly understood. We inv estigated the effects of stimulators of cAMP synthesis on PTHrP releas e by a human lung squamous-carcinoma cell line (BEN). In superfused ce lls grown on microcarrier beads, PTHrP production was significantly in creased after incubation with calcitonin for only 20 min. The release of immunoreactive and bioactive PTHrP was increased by incubating the cells with forskolin, 3-isobutyl-1-methylxanthine or dibutyryl cAMP ev en in the presence of the protein-synthesis inhibitor cycloheximide fo r 6 hr. The calcitonin-mediated stimulation was not accompanied by con comitant changes in PTHrP mRNA. The microfilament-disrupter cytochalas in D was shown to enhance the basal and calcitonin-induced production of PTHrP. These results indicate that stimulators of cAMP synthesis en hanced PTHrP release by BEN cells. (C) 1994 Wiley-Liss, Inc.