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Mouse models of <jats:italic>Helicobacter<\/jats:italic>\u2010induced gastric cancer and colitis\u2010associated colorectal cancer have demonstrated that classical <jats:styled-content style=\"fixed-case\">NF\u2010\u03baB<\/jats:styled-content> signalling is an important regulator of these processes. In the stomach, it has also been demonstrated that signalling involving specific <jats:styled-content style=\"fixed-case\">NF\u2010\u03baB<\/jats:styled-content> proteins, including <jats:styled-content style=\"fixed-case\">NF\u2010\u03baB1<\/jats:styled-content>\/p50, <jats:styled-content style=\"fixed-case\">NF\u2010\u03baB2<\/jats:styled-content>\/p52, and c\u2010Rel, differentially regulate the development of gastric pre\u2010neoplasia. To investigate the effect of <jats:styled-content style=\"fixed-case\">NF\u2010\u03baB<\/jats:styled-content> subunit loss on colitis\u2010associated carcinogenesis, we administered azoxymethane followed by pulsed dextran sodium sulphate to <jats:styled-content style=\"fixed-case\">C57BL<\/jats:styled-content>\/6, <jats:italic>Nfkb1<jats:sup>\u2212\/\u2212<\/jats:sup><\/jats:italic>, <jats:italic>Nfkb2<jats:sup>\u2212\/\u2212<\/jats:sup><\/jats:italic>, and <jats:italic>c\u2010Rel<jats:sup>\u2212\/\u2212<\/jats:sup><\/jats:italic>mice. Animals lacking the <jats:italic>c\u2010Rel<\/jats:italic> subunit were more susceptible to colitis\u2010associated cancer than wild\u2010type mice, developing 3.5 times more colonic polyps per animal than wild\u2010type mice. <jats:italic>Nfkb2<jats:sup>\u2212\/\u2212<\/jats:sup><\/jats:italic> mice were resistant to colitis\u2010associated cancer, developing fewer polyps per colon than wild\u2010type mice (median 1 compared to 4). To investigate the mechanisms underlying these trends, azoxymethane and dextran sodium sulphate were administered separately to mice of each genotype. <jats:italic>Nfkb2<jats:sup>\u2212\/\u2212<\/jats:sup><\/jats:italic> mice developed fewer clinical signs of colitis and exhibited less severe colitis and an attenuated cytokine response compared with all other groups following <jats:styled-content style=\"fixed-case\">DSS<\/jats:styled-content> administration. Azoxymethane administration did not fully suppress colonic epithelial mitosis in <jats:italic>c\u2010Rel<jats:sup>\u2212\/\u2212<\/jats:sup><\/jats:italic> mice and less colonic epithelial apoptosis was also observed in this genotype compared to wild\u2010type counterparts. These observations demonstrate different functions of specific <jats:styled-content style=\"fixed-case\">NF\u2010\u03baB<\/jats:styled-content> subunits in this model of colitis\u2010associated carcinogenesis. <jats:styled-content style=\"fixed-case\">NF\u2010\u03baB2<\/jats:styled-content>\/p52 is necessary for the development of colitis, whilst c\u2010Rel\u2010mediated signalling regulates colonic epithelial cell turnover following <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> damage. \u00a9 2015 The Authors. <jats:italic>The Journal of Pathology<\/jats:italic> published by John Wiley &amp; Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.<\/jats:p>","DOI":"10.1002\/path.4527","type":"journal-article","created":{"date-parts":[[2015,2,26]],"date-time":"2015-02-26T05:43:28Z","timestamp":1424929408000},"page":"326-336","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":49,"title":["<scp>NF\u2010\u03baB1<\/scp>, <scp>NF\u2010\u03baB2<\/scp> and c\u2010Rel differentially regulate susceptibility to colitis\u2010associated adenoma development in <scp>C57BL<\/scp>\/6 mice"],"prefix":"10.1002","volume":"236","author":[{"given":"Michael D","family":"Burkitt","sequence":"first","affiliation":[{"name":"Department of Gastroenterology, Institute of Translational Medicine University of Liverpool  UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdalla F","family":"Hanedi","sequence":"additional","affiliation":[{"name":"Faculty of Medicine University of Tripoli  Tripoli Libya"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carrie A","family":"Duckworth","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Institute of Translational Medicine University of Liverpool  UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan M","family":"Williams","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Institute of Translational Medicine University of Liverpool  UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph M","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Institute of Translational Medicine University of Liverpool  UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorraine A","family":"O'Reilly","sequence":"additional","affiliation":[{"name":"The Walter and Eliza Hall Institute of Medical Research  Melbourne Australia"},{"name":"Department of Medical Biology The University of Melbourne  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