title: Chemokine (C-C) motif ligand 20 is regulated by PGF(2α)-F-prostanoid receptor signalling in endometrial adenocarcinoma and promotes cell proliferation.
abstract: Prostaglandin F(2α) (PGF(2α)) is an inflammatory mediator which signals through a G-protein coupled receptor, the F-prostanoid (FP) receptor. We have previously shown elevated FP receptor expression in endometrial adenocarcinoma, a common gynaecological malignancy in Western countries. In this study, the expression of the chemokine CC motif Ligand 20 (CCL20) was determined to be regulated by PGF(2α)-FP receptor signalling in endometrial adenocarcinoma explants and cell line, and expression of CCL20 and its receptor CCR6 was elevated in endometrial adenocarcinoma compared to non-malignant endometrium. Both CCL20 and CCR6 were localised to neoplastic endometrial epithelial cells. The induction of CCL20 expression by PGF(2α)-FP signalling in an endometrial adenocarcinoma cell line stably expressing the FP receptor (FPS cells) was found to be dependent on the intracellular signalling of Gq, EGFR, ERK, calcineurin and nuclear factor of activated T-cells (NFAT) proteins. The treatment of FPS cells with recombinant CCL20 caused a significant increase in proliferation. Therefore these data demonstrate a role for the FP receptor in regulation of the chemokine CCL20, which can mediate proliferation of endometrial adenocarcinoma epithelial cells.
authors.affiliation: MRC Human Reproductive Sciences Unit The Queen's Medical Research Institute, Edinburgh EH16 4TJ, UK.
authors.forename: Alison E
authors.initials: AE
authors.lastname: Wallace
authors.forename: Rob D
authors.initials: RD
authors.lastname: Catalano
authors.forename: Richard A
authors.initials: RA
authors.lastname: Anderson
authors.forename: Henry N
authors.initials: HN
authors.lastname: Jabbour
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D054418:Chemokine CCL20 / Q000235:genetics* / Q000378:metabolism; D015237:Dinoprost / Q000494:pharmacology; D016889:Endometrial Neoplasms / Q000235:genetics / Q000473:pathology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D008954:Models, Biological; D021381:Protein Transport / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D054399:Receptors, CCR6 / Q000235:genetics / Q000378:metabolism; D011982:Receptors, Prostaglandin / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: C108355:CCL20 protein, human; C106311:CCR6 protein, human; D054418:Chemokine CCL20; D012333:RNA, Messenger; D054399:Receptors, CCR6; D011982:Receptors, Prostaglandin; C034671:prostaglandin F2alpha receptor; D015237:Dinoprost