Expression of cyclooxygenase 2 by prostaglandin E-2 in human endometrial adenocarcinoma cell line HEC-1B

The regulation of expression of cyclooxygenase 2 (COX-2) was investigated b y treatment with PGE(2) in human endometrial adenocarcinoma cell line HEC-1 B. Cine mu M PGE(2) could stimulate the expression of COX-2 approximately t wofold in this cell line. The same concentration of PGE(2) also stimulated activation of mitogen-activated protein kinase (MAP kinase) and protein kin ase B (PKB). PGE(2)-induced MAP kinase activation was sensitive to a MAP ki nase kinase (MEK) inhibitor, PD098059, and a protein kinase A inhibitor, H- 89. PD098059 and H-89 also partially inhibited the expression of COX-2 stim ulated by PGE(2). PGE(2) could stimulate the activation of PKB, which was s ensitive to phosphatidylinositol-3-OH kinase (PI3K) inhibitor, wortmannin. Whereas wortmannin alone partially inhibited the expression of COX-2, a com bination of wortmannin and PD098059 totally inhibited PGE(2)-mediated COX-2 expression. These results suggest that MAP kinase and PI3K pathways are st imulated with PGE(2), and that both of these pathways are involved in the e xpression of COX-2. In addition, the) also suggest that protein kinase A re mains upstream of PGE(2)-induced activation of MAP kinase in HEC-1B cells.