EGF and TPA stimulate de novo synthesis of PGHS-1 and PGHS-2 through different signal transduction pathways

Abstract

Epidermal growth factor (EGF) as well as phorbol 12-myristate 13-acetate (TPA) stimulate de novo synthesis of PGHS (prostaglandin H synthase)-1 and PGHS-2 mRNA, resulting in increased production of PGE 2 in rat tracheal epithelial cells (RTE, EGV-6 cells). Stimulation of PGE 2 production by TPA is more potent than that by EGF. Staurosporine and H-7, protein kinase C (PKC) inhibitors, suppressed the increase of mRNA and PGE 2 levels caused by TPA, but not that caused by EGF. On the other hand, methyl 2,5-dihydroxycinnamate, a tyrosine kinase inhibitor (TKI), suppressed the increase of mRNA and PGE 2 levels caused by EGF, but not that caused by TPA. These results indicate that EGF stimulates de novo synthesis of PGHS-1 and PGHS-2 mRNA through a signal transduction pathway which is independent from PKC-associated mechanisms but dependent upon the tyrosine kinase activity of the EGF receptor.