Journal article

NF-B1, NF-B2 and c-Rel differentially regulate susceptibility to colitis-associated adenoma development in C57BL/6 mice

Michael D Burkitt, Abdalla F Hanedi, Carrie A Duckworth, Jonathan M Williams, Joseph M Tang, Lorraine A O'Reilly, Tracy L Putoczki, Steve Gerondakis, Rod Dimaline, Jorge H Caamano, D Mark Pritchard

JOURNAL OF PATHOLOGY | WILEY | Published : 2015

Abstract

NF-κB signalling is an important factor in the development of inflammation-associated cancers. Mouse models of Helicobacter-induced gastric cancer and colitis-associated colorectal cancer have demonstrated that classical NF-κB signalling is an important regulator of these processes. In the stomach, it has also been demonstrated that signalling involving specific NF-κB proteins, including NF-κB1/p50, NF-κB2/p52, and c-Rel, differentially regulate the development of gastric pre-neoplasia. To investigate the effect of NF-κB subunit loss on colitis-associated carcinogenesis, we administered azoxymethane followed by pulsed dextran sodium sulphate to C57BL/6, Nfkb1(-/-), Nfkb2(-/-), and c-Rel(-/-)..

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Grants

Awarded by Wellcome Trust


Awarded by European Community


Awarded by Cancer Council New South Wales


Awarded by NHMRC Program


Awarded by Independent Research Institutes Infrastructure Support Scheme


Awarded by BBSRC


Awarded by Biotechnology and Biological Sciences Research Council


Awarded by National Institute for Health Research


Funding Acknowledgements

We would like to thank Professor ME White (University of Manchester, UK) and Professor Andreas Strasser (The Walter and Eliza Hall Institute of Medical Research) for insightful discussions and Ann Lin (The Walter and Eliza Hall Institute of Medical Research) for technical assistance. We are also grateful to Bristol-Myers Squibb for providing the Nfkb2<SUP>-/-</SUP> mice, to H-C Liou for providing the c-Rel<SUP>-/-</SUP> mice, and to D Baltimore for the Nfkb1<SUP>-/-</SUP> mice. The work represented in this article was supported with funds from the following sources: Wellcome Trust Research Training Fellowship awarded to MDB (grant No WT083823AIA); Wellcome Trust Institutional Strategic Support Fund / University of Liverpool Fellowship awarded to MDB; PhD studentship funded by the Libyan Higher Education Ministry to AFH. JW and DMP were supported by the European Community's Seventh Framework Programme (FP7/2007-2013) under grant agreement No 305564 (SysmedIBD). JC was supported by the EU FP7 Integrated Project INFLACARE and the College of Medical and Dental Sciences, University of Birmingham. LOR and TP were supported by a project grant from the Cancer Australia funding partner, Cancer Council New South Wales, No 1047672. SG was supported by NHMRC Program grant No 10167019. LOR and TP were also supported by the Independent Research Institutes Infrastructure Support Scheme (grant No 361646) and the Victorian State Government (OIS grant).