This Article Full Text Full Text (PDF) All Versions of this Article: 148/8/3635    most recent Author Manuscript (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Sales, K. J. Articles by Jabbour, H. N. Search for Related Content PubMed PubMed Citation Articles by Sales, K. J. Articles by Jabbour, H. N. Pubmed/NCBI databases Gene GEO Profiles HomoloGene Nucleotide Protein UniGene Compound via MeSH Substance via MeSH Hazardous Substances DB PROSTAGLANDIN F2ALPHA

F-Prostanoid Receptor Regulation of Fibroblast Growth Factor 2 Signaling in Endometrial Adenocarcinoma Cells

Medical Research Council Human Reproductive Sciences Unit (K.J.S., S.C.B., R.A.A., H.N.J.), The Queen’s Medical Research Institute, Department of Pathology (A.R.W.W.), and Division of Reproductive and Developmental Sciences (R.A.A.), University of Edinburgh, Edinburgh, Scotland EH16 4TJ, United Kingdom

Address all correspondence and requests for reprints to: Dr. Henry N. Jabbour, Medical Research Council Human Reproductive Sciences Unit, The Queen’s Medical Research Institute, 47 Little France Crescent, Edinburgh, Scotland EH16 4TJ, United Kingdom. E-mail: h.jabbour{at}hrsu.mrc.ac.uk.

Prostaglandin (PG) F₂ is a potent bioactive lipid in the female reproductive tract, and exerts its function after coupling with its heptahelical G-protein-coupled receptor [F-series-prostanoid (FP) receptor] to initiate cell signaling and target gene transcription. In the present study, we found elevated expression of fibroblast growth factor (FGF) 2, FGF receptor 1 (FGFR1), and FP receptor, colocalized within the neoplastic epithelial cells of endometrial adenocarcinomas. We investigated a role for PGF₂-FP receptor interaction in modulating FGF2 expression and signaling using an endometrial adenocarcinoma cell line stably expressing the FP receptor to the levels detected in endometrial adenocarcinomas (FPS cells) and endometrial adenocarcinoma tissue explants. PGF₂-FP receptor activation rapidly induced FGF2 mRNA expression, and elevated FGF2 protein expression and secretion into the culture medium in FPS cells and endometrial adenocarcinoma explants. The effect of PGF₂ on the expression and secretion of FGF2 could be abolished by treatment of FPS cells and endometrial tissues with an FP receptor antagonist (AL8810) and inhibitor of ERK (PD98059). Furthermore, we have shown that FGF2 can promote the expression of FGF2 and cyclooxygenase-2, and enhance proliferation of endometrial adenocarcinoma cells via the FGFR1 and ERK pathways, thereby establishing a positive feedback loop to regulate neoplastic epithelial cell function in endometrial adenocarcinomas.