| First Author | Burkitt MD | Year | 2013 |
| Journal | Oncogene | Volume | 32 |
| Issue | 50 | Pages | 5563-73 |
| PubMed ID | 23975431 | Mgi Jnum | J:205159 |
| Mgi Id | MGI:5544167 | Doi | 10.1038/onc.2013.334 |
| Citation | Burkitt MD, et al. (2013) Signaling mediated by the NF-kappaB sub-units NF-kappaB1, NF-kappaB2 and c-Rel differentially regulate Helicobacter felis-induced gastric carcinogenesis in C57BL/6 mice. Oncogene 32(50):5563-73 |
| abstractText | The classical nuclear factor-kappaB (NF-kappaB) 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-kappaB signaling in the gastric epithelium led to the development of increased preneoplastic pathology, however the role of specific NF-kappaB 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-kappaB1- and NF-kappaB2-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. |
