| First Author | Syu LJ | Year | 2012 |
| Journal | Am J Pathol | Volume | 181 |
| Issue | 6 | Pages | 2114-25 |
| PubMed ID | 23036899 | Mgi Jnum | J:190387 |
| Mgi Id | MGI:5448778 | Doi | 10.1016/j.ajpath.2012.08.017 |
| Citation | Syu LJ, et al. (2012) Transgenic expression of interferon-gamma in mouse stomach leads to inflammation, metaplasia, and dysplasia. Am J Pathol 181(6):2114-25 |
| abstractText | Gastric adenocarcinoma is one of the leading causes of cancer mortality worldwide. It arises through a stepwise process that includes prominent inflammation with expression of interferon-gamma (IFN-gamma) and multiple other pro-inflammatory cytokines. We engineered mice expressing IFN-gamma under the control of the stomach-specific H(+)/K(+) ATPase beta promoter to test the potential role of this cytokine in gastric tumorigenesis. Stomachs of H/K-IFN-gamma transgenic mice exhibited inflammation, expansion of myofibroblasts, loss of parietal and chief cells, spasmolytic polypeptide expressing metaplasia, and dysplasia. Proliferation was elevated in undifferentiated and metaplastic epithelial cells in H/K-IFN-gamma transgenic mice, and there was increased apoptosis. H/K-IFN-gamma mice had elevated levels of mRNA for IFN-gamma target genes and the pro-inflammatory cytokines IL-6, IL-1beta, and tumor necrosis factor-alpha. Intracellular mediators of IFN-gamma and IL-6 signaling, pSTAT1 and pSTAT3, respectively, were detected in multiple cell types within stomach. H/K-IFN-gamma mice developed dysplasia as early as 3 months of age, and 4 of 39 mice over 1 year of age developed antral polyps or tumors, including one adenoma and one adenocarcinoma, which expressed high levels of nuclear beta-catenin. Our data identified IFN-gamma as a pivotal secreted factor that orchestrates complex changes in inflammatory, epithelial, and mesenchymal cell populations to drive pre-neoplastic progression in stomach; however, additional alterations appear to be required for malignant conversion. |
