Mitogen-activated protein kinase activation and regulation of cyclooxygenase 2 expression by platelet-activating factor and hCG in human endometrial adenocarcinoma cell line HEC-1B

The activation of mitogen-activated protein kinase (MAP kinase) and the reg ulation of cyclooxygenase 2 (COX-2) were investigated in the human endometr ial adenocarcinoma cell line HEC-1B by treatment with platelet-activating f actor (PAF) and hCG. Pretreatment of the cells with both oestradiol and med roxyprogesterone acetate was required for MAP kinase activation and COX-2 e xpression to respond to PAF and hCG. PAF-induced MAP kinase activation was sensitive to MAP kinase kinase (MEK) inhibitor, PD098059, and phosphatidyli nositol-3-OH kinase (PI3K) inhibitor, wortmannin. In contrast, hCG-induced MAP kinase activation was sensitive to PD098059 and protein kinase A inhibi tor, H-89, but not to wortmannin. PAF-induced COX-2 expression was insensit ive to PD098059 but sensitive to wortmannin, whereas hCG-induced COX-2 expr ession was sensitive to PD098059 and H-89 but insensitive to wortmannin. 8- (4-chlorophenylthio)-cAMP, a potent cAMP analogue, induced activation of MA P kinase and expression of COX-2. These results indicate that MAP kinase is activated with PAF and hCG in HEC-1B cells. In addition, COX-2 expression is stimulated through the MAP kinase activation pathway with hCG and the wo rtmannin sensitive pathway with PAF in HEC-1B cells. These results also imp ly that protein kinase A remains upstream of hCG-induced activation of MAP kinase in HEC-1B cells.