EGF AND TPA STIMULATE DE-NOVO SYNTHESIS OF PGHS-1 AND PGHS-2 THROUGH DIFFERENT SIGNAL-TRANSDUCTION PATHWAYS

Epidermal growth factor (EGF) as well as phorbol 12-myristate 13-aceta te (TPA) stimulate de novo synthesis of PGHS (prostaglandin H synthase )-1 and PGHS-2 mRNA, resulting in increased production of PGE, in rat tracheal epithelial cells (RTE, EGV-6 cells), Stimulation of PGE(2) pr oduction by TPA is more potent than that by EGF, Staurosporine and H-7 , protein kinase C (PKC) inhibitors, suppressed the increase of mRNA a nd PGE(2) levels caused by TPA, but not that caused by EGF. On the oth er hand, methyl 2,5-dihydroxycinnamate, a tyrosine kinase inhibitor (T KI), 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 transduc tion pathway which is independent from PKC-associated mechanisms but d ependent upon the tyrosine kinase activity of the EGF receptor.