epidermal-growth-factor and 9-hydroxy-10-12-octadecadienoic-acid

Topics: Animals; Arachidonic Acid; Cell Division; Cells, Cultured; Cricetinae; Cyclooxygenase 1; Cyclooxygenase 2; Embryo, Mammalian; Epidermal Growth Factor; Fibroblasts; Isoenzymes; Linoleic Acid; Linoleic Acids; Linoleic Acids, Conjugated; Mesocricetus; Prostaglandin-Endoperoxide Synthases; RNA, Messenger; Transcription, Genetic

Topics: 12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; Animals; Cell Division; Cell Line; Cricetinae; DNA; DNA Replication; Embryo, Mammalian; Epidermal Growth Factor; Hydroxyeicosatetraenoic Acids; Linoleic Acids; Linoleic Acids, Conjugated; Mesocricetus; Oxidation-Reduction; Thymidine

Epidermal growth factor (EGF) stimulates DNA synthesis in quiescent Syrian hamster embryo (SHE) cells. Work in the present authors' laboratory has shown that the formation of 9- and 13-hydroxyoctadecadienoic acid (HODEs), 15-lipoxygenase-derived metabolites of linoleic acid, are involved in the mitogenic response to EGF in these cells (Glasgow et al. (1992) J. Biol. Chem. 267, 10771-10779). SHE cells also produce prostaglandin E2 (PGE2) and prostaglandin F2 alpha (PGF2 alpha). We now report the effects of HODEs and prostaglandins on EGF-dependent expression of the growth-related proto-oncogene c-myc in SHE cells. Treatment of cells with eicosatetraynoic acid (ETYA), which blocks EGF-dependent HODE formation, inhibited the mitogenic response to EGF, while exogenous 13-HODE potentiated EGF-dependent DNA synthesis. However, neither ETYA or 13-HODE altered the accumulation of c-myc mRNA in response to EGF. In contrast, PGE2 inhibited EGF-induced DNA synthesis and down-regulated EGF-stimulated c-myc mRNA accumulation in a dose-dependent manner, whereas PGF2 alpha had no effect on these responses. PGE2, but not PGF2 alpha, induced a rapid increase in cAMP formation, and both forskolin and 8-(4-chlorophenylthio)-cAMP mimicked the inhibitory effects of PGE2 on EGF-dependent DNA synthesis and c-myc mRNA accumulation, suggesting that the involvement of cAMP. The results indicate that the modulation of EGF-dependent DNA synthesis by PGE2, but not by HODEs, is associated with altered expression of the proto-oncogene c-myc in SHE cells.

Topics: Animals; Cell Line; Cricetinae; Cricetulus; DNA; Epidermal Growth Factor; Genes, myc; Linoleic Acids; Linoleic Acids, Conjugated; Prostaglandins; Proto-Oncogene Proteins c-myc

Topics: Animals; Cell Division; Cell Line; DNA; Epidermal Growth Factor; Fibroblasts; Linoleic Acid; Linoleic Acids; Linoleic Acids, Conjugated; Lipoxygenase; Mice; Mice, Inbred BALB C; Signal Transduction