title: Prostaglandin E2 and F2alpha activate the FP receptor and up-regulate cyclooxygenase-2 expression via the cyclic AMP response element.
abstract: In endometrial adenocarcinomas COX-2 and F-series prostanoid (FP) receptor expression and prostanoid biosynthesis (PGE(2) and PGF(2alpha)) are elevated. In the present study, we investigated the effect of PGE(2) and PGF(2alpha) 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 PGE(2) and PGF(2alpha) can mobilize inositol 1,4,5-trisphosphate, induce ERK1/2 phosphorylation via the phospholipase Cbeta-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 PGE(2) or PGF(2alpha)-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 PGE(2) and PGF(2alpha) biosynthesized locally within endometrial adenocarcinomas can regulate tumor cell function in an autocrine/paracrine manner via the FP receptor.
authors.affiliation: MRC Human Reproductive Sciences Unit, The Queen's Medical Research Institute, 47 Little France Crescent, Old Dalkeith Road, Edinburgh, United Kingdom.
authors.forename: Kurt J
authors.initials: KJ
authors.lastname: Sales
authors.forename: Vivien
authors.initials: V
authors.lastname: Grant
authors.forename: Henry N
authors.initials: HN
authors.lastname: Jabbour
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism; D045744:Cell Line, Tumor; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism*; D015237:Dinoprost / Q000031:analogs & derivatives / Q000378:metabolism*; D015232:Dinoprostone / Q000378:metabolism*; D016889:Endometrial Neoplasms / Q000378:metabolism; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D017930:Genes, Reporter; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011448:Prostaglandin Antagonists / Q000378:metabolism; D011982:Receptors, Prostaglandin / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D018078:Receptors, Prostaglandin E / Q000378:metabolism; D020218:Response Elements; D015398:Signal Transduction / Q000502:physiology*; D044004:Xanthones / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D011448:Prostaglandin Antagonists; D011982:Receptors, Prostaglandin; D018078:Receptors, Prostaglandin E; D044004:Xanthones; C034671:prostaglandin F2alpha receptor; C121227:AL 8810; C053876:6-isopropoxy-9-oxoxanthene-2-carboxylic acid; D015544:Inositol 1,4,5-Trisphosphate; D015237:Dinoprost; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D048049:Extracellular Signal-Regulated MAP Kinases; D015232:Dinoprostone