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.
Original language | English |
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Pages (from-to) | 5563-73 |
Number of pages | 11 |
Journal | Oncogene |
Volume | 32 |
Issue number | 50 |
DOIs | |
Publication status | Published - 12 Dec 2013 |
Keywords
- Animals
- Cell Transformation, Neoplastic/metabolism
- Disease Models, Animal
- Female
- Gastric Mucosa/metabolism
- Gene Deletion
- Helicobacter Infections/complications
- Helicobacter felis
- Inflammation/genetics
- Mice
- Mice, Knockout
- NF-kappa B/chemistry
- NF-kappa B p50 Subunit/genetics
- NF-kappa B p52 Subunit/genetics
- Proto-Oncogene Proteins c-rel/metabolism
- Signal Transduction
- Stomach Neoplasms/etiology