title: Signaling mediated by the NF-κB sub-units NF-κB1, NF-κB2 and c-Rel differentially regulate Helicobacter felis-induced gastric carcinogenesis in C57BL/6 mice.
abstract: The classical nuclear factor-kappaB (NF-κB) signaling pathway has been shown to be important in a number of models of inflammation-associated cancer. In a mouse model of Helicobacter-induced gastric cancer, impairment of classical NF-κB signaling in the gastric epithelium led to the development of increased preneoplastic pathology, however the role of specific NF-κB proteins in Helicobacter-associated gastric cancer development remains poorly understood. To investigate this C57BL/6, Nfkb1(-/-), Nfkb2(-/-) and c-Rel(-/-) mice were infected with Helicobacter felis for 6 weeks or 12 months. Bacterial colonization, gastric atrophy and preneoplastic changes were assessed histologically and cytokine expression was assessed by qPCR. Nfkb1(-/-) mice developed spontaneous gastric atrophy when maintained for 12 months in conventional animal house conditions. They also developed more pronounced gastric atrophy after short-term H. felis colonization with a similar extent of preneoplasia to wild-type (WT) mice after 12 months. c-Rel(-/-) mice developed a similar degree of gastric atrophy to WT mice; 3 of 6 of these animals also developed lymphoproliferative lesions after 12 months of infection. Nfkb2(-/-) mice developed minimal gastric epithelial pathology even 12 months after H. felis infection. These findings demonstrate that NF-κB1- and NF-κB2-mediated signaling pathways differentially regulate the epithelial consequences of H. felis infection in the stomach, while c-Rel-mediated signaling also appears to modulate the risk of lymphomagenesis in gastric mucosa-associated lymphoid tissue.
authors: Department of Gastroenterology, The Henry Wellcome Laboratories, Institute of Translational Medicine, University of Liverpool, Liverpool, UK.
authors: M D
authors: 0000000250556408
authors: MD
authors: Burkitt
authors: Department of Gastroenterology, The Henry Wellcome Laboratories, Institute of Translational Medicine, University of Liverpool, Liverpool, UK.
authors: J M
authors: JM
authors: Williams
authors: Department of Gastroenterology, The Henry Wellcome Laboratories, Institute of Translational Medicine, University of Liverpool, Liverpool, UK.
authors: C A
authors: CA
authors: Duckworth
authors: Department of Gastroenterology, The Henry Wellcome Laboratories, Institute of Translational Medicine, University of Liverpool, Liverpool, UK.
authors: A
authors: A
authors: O'Hara
authors: Department of Gastroenterology, The Henry Wellcome Laboratories, Institute of Translational Medicine, University of Liverpool, Liverpool, UK.
authors: A
authors: A
authors: Hanedi
authors: Department of Cellular and Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Liverpool, UK.
authors: A
authors: A
authors: Varro
authors: IBR-School of Immunity and Infection, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK.
authors: J H
authors: JH
authors: Caamaño
authors: Department of Gastroenterology, The Henry Wellcome Laboratories, Institute of Translational Medicine, University of Liverpool, Liverpool, UK.
authors: D M
authors: DM
authors: Pritchard
mesh_terms: D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D017353:Gene Deletion; D016481:Helicobacter Infections / Q000150:complications / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D044922:Helicobacter felis; D007249:Inflammation / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D016328:NF-kappa B / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D052002:NF-kappa B p50 Subunit / Q000235:genetics / Q000378:metabolism; D052003:NF-kappa B p52 Subunit / Q000235:genetics / Q000378:metabolism; D020569:Proto-Oncogene Proteins c-rel / Q000378:metabolism*; D015398:Signal Transduction; D013274:Stomach Neoplasms / Q000209:etiology / Q000378:metabolism*
chemical_list: D016328:NF-kappa B; D052002:NF-kappa B p50 Subunit; D052003:NF-kappa B p52 Subunit; D020569:Proto-Oncogene Proteins c-rel
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