Prostaglandin E2 stimulates Fas ligand expression via the EP1 receptor in colon cancer cells

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dc.contributor.authorO'Callagan, Grace
dc.contributor.authorKelly, Jacquie
dc.contributor.authorShanahan, Fergus
dc.contributor.authorHouston, Aileen M.
dc.contributor.funderHealth Research Boarden
dc.contributor.funderScience Foundation Irelanden
dc.date.accessioned2019-09-04T14:38:07Z
dc.date.available2019-09-04T14:38:07Z
dc.date.issued2008-08-05
dc.date.updated2019-09-02T06:32:21Z
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 E2 (PGE2), 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 PGE2 increased FasL expression and these cells showed increased cytotoxicity against Fas-sensitive Jurkat T cells. Prostaglandin E2-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 PGE2 positively regulates FasL expression in colon tumour cells, adding another pro-neoplastic activity to PGE2.en
dc.description.sponsorshipScience Foundation Ireland (no. 5087115226)en
dc.description.statusPeer revieweden
dc.description.versionPublished Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationO'Callaghan, G., Kelly, J., Shanahan, F. and Houston, A. (2008) 'Prostaglandin E2 stimulates Fas ligand expression via the EP1 receptor in colon cancer cells', British Journal Of Cancer, 99, pp. 502-512. doi: 10.1038/sj.bjc.6604490en
dc.identifier.doi10.1038/sj.bjc.6604490en
dc.identifier.endpage512en
dc.identifier.issn0007-0920
dc.identifier.journaltitleBritish Journal of Canceren
dc.identifier.startpage502en
dc.identifier.urihttps://hdl.handle.net/10468/8451
dc.identifier.volume99en
dc.language.isoenen
dc.publisherSpringer Natureen
dc.relation.urihttps://www.nature.com/articles/6604490
dc.rights© 2008 Cancer Research UK. From twelve months after its original publication, this work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/en
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/3.0/en
dc.subjectFas liganden
dc.subjectProstaglandin E2en
dc.subjectRegulationen
dc.subjectTumour immune evasionen
dc.subjectColorectal Canceren
dc.subjectCarcinomaen
dc.subjectInduced apoptosisen
dc.subjectImmune privilegeen
dc.subjectSubtype EP1en
dc.subjectCyclooxygenase 2en
dc.subjectCounterattacken
dc.titleProstaglandin E2 stimulates Fas ligand expression via the EP1 receptor in colon cancer cellsen
dc.typeArticle (peer-reviewed)en
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