Prostaglandin E2 and F2α activate the FP receptor and up-regulate cyclooxygenase-2 expression via the cyclic AMP response element

In endometrial adenocarcinomas COX-2 and F-series prostanoid (FP) receptor expression and prostanoid biosynthesis (PGE2 and PGF2α) are elevated. In the present study, we investigated the effect of PGE2 and PGF2α on the expression of COX-2 via the FP receptor in endometrial adenocarcinoma cells stably expressing the FP receptor (FPS cells). Using chemical inhibitors of intracellular signaling pathways, reporter gene assays and quantitative RT-PCR analysis, we show that PGE2 and PGF2α can mobilize inositol 1,4,5-trisphosphate, induce ERK1/2 phosphorylation via the phospholipase Cβ-protein kinase A-epidermal growth factor receptor pathway and induce cyclooxygenase-2 (COX-2) expression via the FP receptor. In addition we show that the PGE2 or PGF2α-regulation of COX-2 via the FP receptor is mediated via the cAMP response element (CRE) binding site on the COX-2 promoter. These data indicate that PGE2 and PGF2α biosynthesized locally within endometrial adenocarcinomas can regulate tumor cell function in an autocrine/paracrine manner via the FP receptor.