Parathyroid hormone-related protein (PTHrP) inhibits proliferation of Chinese hamster ovary cells stably transfected with a PTH/PTHrP receptor cDNA

The effect of parathyroid hormone-related protein (PTHrP) on proliferation was examined in chinese hamster ovary (CHO) cells transfected with a PTH/PTHrP receptor encoding cDNA. Treatment with chicken PTHrP(1–36) (chPTHrP) lowered the cell number to 49±2% of untreated controls after 6 days with a half-maximal effect at 1 nM. The effect was mimicked by human (h) PTH(1–34), Br-cAMP and forskolin, but not by the receptor antagonist hPTH(3–34). Reduction of cell number was accompanied by increased PTH/PTHrP receptor expression and persistently activated adenylyl cyclase, together with altered cell morphology from epithelial to spindle-like forms, clustered growth and increased phosphate uptake. chPTHrP increased [Ca 2+ ] i , but failed to activate membrane bound protein kinase C (PKC). Pretreatment with chPTHrP did not affect phorbol ester stimulated PKC activity, and chPTHrP or serum evoked increases in [Ca 2+ ]. In conclusion, PTHrP induced inhibition of proliferation and altered cell morphology is mediated by increased adenylyl cyclase rather than by PKC-dependent mechanisms in CHO cells.