The tumor promoters 12-O-tetradecanoylphorbol-13-acetate and okadaic acid differ in toxicity, mitogenic activity and induction of gene expression

Okadaic acid (OA) and 12-O-tetradecanoylphorbol-13-acetate (TPA)are both potent tumor promoters in a mouse skin carcinogenesisexperiment. OA was much more toxic than TPA for murine embryocell lines such as Swiss 3T3 cells or C3H10T? cells. TPA isa potent mitogen for 3T3 cells; in contrast OA was unable tostimulate DNA synthesis in these cells. TPA induces a familyof primary response genes, the TPA induced sequence (TIS) genes,in a wide variety of cells. Although OA induced modest levelsof TIS mRNA expression, the time course of the induction ofTIS1 and TIS8 mRNA was delayed when compared to induction byTPA or peptide mitogeas such as fibroblast growth factor (FGF).In addition TPA-mediated down-regulation of protein kinase Cattenuated TIS gene induction by OA, but not by FGF.