Protein kinase C-induced stimulation or inhibition of cellular proliferation in a murine macrophage tumor cell line

M5076, a tumorigenic murine macrophage cell line, demonstrates diverse proliferative responses to a panel of protein kinase C activators. Thus, the tumor-promoting phorbol ester 12-O-tetradecanoylphorbol-13-acetate and mezerein potently inhibit cellular proliferation (by greater than 90%), whereas the diacylglycerol analogue 1-oleoyl-2-acetyl-sn-glycerol markedly stimulates proliferation of serum-starved, quiescent M5076 cells. Another DG analogue, 1,2-dioctanoyl-sn-glycerol, has no effect on growth. However, all of these agents induce expression of c-fos oncogene mRNA levels to a similar magnitude and activate protein kinase C as determined by Mr 80,000 phosphorylation. Levels of c-fos protein induced by these treatments were markedly different with the antiproliferative agents producing greater c-fos protein levels.