PARATHYROID HORMONE-RELATED PROTEIN (PTHRP) INHIBITS PROLIFERATION OFCHINESE-HAMSTER OVARY CELLS STABLY TRANSFECTED WITH A PTH PTHRP RECEPTOR CDNA/

The effect of parathyroid hormone-related protein (PTHrP) on prolifera tion was examined in chinese hamster ovary (CHO) cells transfected wit h a PTH/PTHrP receptor encoding cDNA. Treatment with chicken PTHrP(1-3 6) (chPTHrP) lowered the cell number to 49 +/- 2% of untreated control s after 6 days with a half-maximal effect at 1 nM. The effect was mimi cked by human (h) PTH(1-34), Br-cAMP and forskolin, but not by the rec eptor 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 epithelia l to spindle-like forms, clustered growth and increased phosphate upta ke. chPTHrP increased [Ca2+](i), but failed to activate membrane bound protein kinase C (PKC). Pretreatment with chPTHrP did not affect phor bol ester stimulated PKC activity, and chPTHrP or serum evoked increas es in [Ca2+](i). In conclusion, PTHrP induced inhibition of proliferat ion and altered cell morphology is mediated by increased adenylyl cycl ase rather than by PKC-dependent mechanisms in CHO cells. (C) 1997 Els evier Science Ireland Ltd.