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 PGF2 alpha) are elevated. In the present study, we investigated the effect of PGE2 and PGF2 alpha 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 PGF2 alpha can mobilize inositol 1,4,5-trisphosphate, induce ERK1/2 phosphorylation via the phospholipase C beta-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 PGF2 alpha-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 PGF2 alpha biosynthesized locally within endometrial adenocarcinomas can regulate tumor cell function in an autocrine/paracrine manner via the FP receptor. (c) 2008 Elsevier Ireland Ltd. All fights reserved.