Signaling mediated by the NF-[kappa]B sub-units NF-[kappa]B1, NF-[kappa]B2 and c-Rel differentially regulate Helicobacter felis-induced gastric carcinogenesis in C57BL/6 mice

• Published in: Oncogene Vol. 32; no. 50; p. 5563
• Main Authors: Burkitt, M D, Williams, J M, Duckworth, C A, O'hara, A, Hanedi, A, Varro, A, Caamaño, J H, Pritchard, D M
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group 12.12.2013
• Subjects: Bacteria; Cancer; Gastroenterology; Rodents; Signaling
• DOI: 10.1038/onc.2013.334
• ISSN: 0950-9232

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.