POTENTIATION OF K252A, A PROTEIN-KINASE INHIBITOR-INDUCED POLYPLOIDIZATION BY CAMP IN CULTURED FIBROSARCOMA CELL-LINE

We found that K252a, a potent inhibitor of protein kinases (PK), induced DNA rereplication of Meth-A cells, i.e., DNA synthesis at a higher DNA ploidy without undergoing cytokinesis (polyploidization). The K252a-induced polyploidization was inhibited by phorbol 12-myristate 13-acetate (PMA), a protein kinase C (PKC) activator, suggesting that the polyploidization is caused through inhibition of PKC. By contrast, the polyploidization was potentiated by adenosine 3':5'-cyclic monophosphate (cAMP), a cAMP-dependent protein kinase (PKA) activator. These findings suggest that the cAMP-dependent signaling pathway and diacylglycerol (DAG)-dependent signaling pathway play an important role in regulating the induction of polyploidization in Meth-A cells, through a possible ''cross-talk'' between the two pathways. (C) 1994 Academic Press, Inc.