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dc.contributor.authorO'Callaghan, G
dc.contributor.authorKelly, J
dc.contributor.authorShanahan, F
dc.contributor.authorHouston, A
dc.date.accessioned2012-02-03T15:06:06Z
dc.date.available2012-02-03T15:06:06Z
dc.date.issued2012-02-03T15:06:06Z
dc.identifier.citationBr J Cancer. 2008 Aug 5;99(3):502-12. Epub 2008 Jul 22.en_GB
dc.identifier.issn1532-1827 (Electronic)en_GB
dc.identifier.issn0007-0920 (Linking)en_GB
dc.identifier.pmid18648368en_GB
dc.identifier.doi10.1038/sj.bjc.6604490en_GB
dc.identifier.urihttp://hdl.handle.net/10147/208873
dc.description.abstractFas ligand (FasL/CD95L) is a member of the tumour necrosis factor superfamily that triggers apoptosis following crosslinking of the Fas receptor. Despite studies strongly implicating tumour-expressed FasL as a major inhibitor of the anti-tumour immune response, little is known about the mechanisms that regulate FasL expression in tumours. In this study, we show that the cyclooxygenase (COX) signalling pathway, and in particular prostaglandin E(2) (PGE(2)), plays a role in the upregulation of FasL expression in colon cancer. Suppression of either COX-2 or COX-1 by RNA interference in HCA-7 and HT29 colon tumour cells reduced FasL expression at both the mRNA and protein level. Conversely, stimulation with PGE(2) increased FasL expression and these cells showed increased cytotoxicity against Fas-sensitive Jurkat T cells. Prostaglandin E(2)-induced FasL expression was mediated by signalling via the EP1 receptor. Moreover, immunohistochemical analysis using serial sections of human colon adenocarcinomas revealed a strong positive correlation between COX-2 and FasL (r=0.722; P<0.0001) expression, and between EP1 receptor and FasL (r=0.740; P<0.0001) expression, in the tumour cells. Thus, these findings indicate that PGE(2) positively regulates FasL expression in colon tumour cells, adding another pro-neoplastic activity to PGE(2).
dc.language.isoengen_GB
dc.subject.meshBlotting, Westernen_GB
dc.subject.meshCell Line, Tumoren_GB
dc.subject.meshCoculture Techniquesen_GB
dc.subject.meshColonic Neoplasms/*metabolism/pathologyen_GB
dc.subject.meshDinoprostone/*pharmacologyen_GB
dc.subject.meshEnzyme-Linked Immunosorbent Assayen_GB
dc.subject.meshFas Ligand Protein/genetics/*metabolismen_GB
dc.subject.meshFluorescent Antibody Techniqueen_GB
dc.subject.meshHumansen_GB
dc.subject.meshRNA Interferenceen_GB
dc.subject.meshRNA, Messenger/geneticsen_GB
dc.subject.meshReceptors, Prostaglandin E/*metabolismen_GB
dc.subject.meshReceptors, Prostaglandin E, EP1 Subtypeen_GB
dc.subject.meshSignal Transductionen_GB
dc.titleProstaglandin E2 stimulates Fas ligand expression via the EP1 receptor in colon cancer cells.en_GB
dc.contributor.departmentDepartment of Medicine, University College Cork, National University of Ireland, , Clinical Science Building, Cork University Hospital, Wilton, Cork, Ireland.en_GB
dc.identifier.journalBritish journal of canceren_GB
dc.description.provinceMunster
html.description.abstractFas ligand (FasL/CD95L) is a member of the tumour necrosis factor superfamily that triggers apoptosis following crosslinking of the Fas receptor. Despite studies strongly implicating tumour-expressed FasL as a major inhibitor of the anti-tumour immune response, little is known about the mechanisms that regulate FasL expression in tumours. In this study, we show that the cyclooxygenase (COX) signalling pathway, and in particular prostaglandin E(2) (PGE(2)), plays a role in the upregulation of FasL expression in colon cancer. Suppression of either COX-2 or COX-1 by RNA interference in HCA-7 and HT29 colon tumour cells reduced FasL expression at both the mRNA and protein level. Conversely, stimulation with PGE(2) increased FasL expression and these cells showed increased cytotoxicity against Fas-sensitive Jurkat T cells. Prostaglandin E(2)-induced FasL expression was mediated by signalling via the EP1 receptor. Moreover, immunohistochemical analysis using serial sections of human colon adenocarcinomas revealed a strong positive correlation between COX-2 and FasL (r=0.722; P<0.0001) expression, and between EP1 receptor and FasL (r=0.740; P<0.0001) expression, in the tumour cells. Thus, these findings indicate that PGE(2) positively regulates FasL expression in colon tumour cells, adding another pro-neoplastic activity to PGE(2).


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