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 carcinogenesis experiment. OA was much more toxic than TPA for murine embryo cell lines such as Swiss 3T3 cells or C3H10T1/2 cells. TPA is a potent mitogen for 3T3 cells; in contrast OA was unable to stimulate DNA synthesis in these cells. TPA induces a family of primary response genes, the TPA induced sequence (TIS) genes, in a wide variety of cells. Although OA induced modest levels of TIS mRNA expression, the time course of the induction of TIS1 and TIS8 mRNA was delayed when compared to induction by TPA or peptide mitogens such as fibroblast growth factor (FGF). In addition TPA-mediated down-regulation of protein kinase C attenuated TIS gene induction by OA, but not by FGF.
Herschman
H R
HR
Department of Biological Chemistry, UCLA Center for the Health Sciences 90024.
Lim
R W
RW
Brankow
D W
DW
Fujiki
H
H
D000818:Animals; D002273:Carcinogens / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects*; D002478:Cells, Cultured; D004261:DNA Replication / Q000187:drug effects*; D004988:Ethers, Cyclic / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D007700:Kinetics; D051379:Mice; D019319:Okadaic Acid; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D013936:Thymidine / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects*; D015533:Transcriptional Activation
D002273:Carcinogens; D004988:Ethers, Cyclic; D012333:RNA, Messenger; D019319:Okadaic Acid; D013755:Tetradecanoylphorbol Acetate; D013936:Thymidine