| First Author | Tu SP | Year | 2011 |
| Journal | Cancer Res | Volume | 71 |
| Issue | 12 | Pages | 4247-59 |
| PubMed ID | 21512143 | Mgi Jnum | J:173758 |
| Mgi Id | MGI:5050332 | Doi | 10.1158/0008-5472.CAN-10-4009 |
| Citation | Tu SP, et al. (2011) IFN-{gamma} Inhibits Gastric Carcinogenesis by Inducing Epithelial Cell Autophagy and T-Cell Apoptosis. Cancer Res 71(12):4247-4259 |
| abstractText | IFN-gamma mediates responses to bacterial infection and autoimmune disease, but it is also an important tumor suppressor. It is upregulated in the gastric mucosa by chronic Helicobacter infection; however, whether it plays a positive or negative role in inflammation-associated gastric carcinogenesis is unexplored. To study this question, we generated an H(+)/K(+)-ATPase-IFN-gamma transgenic mouse that overexpresses murine IFN-gamma in the stomach mucosa. In contrast to the expected proinflammatory role during infection, we found that IFN-gamma overexpression failed to induce gastritis and instead inhibited gastric carcinogenesis induced by interleukin-1beta (IL-1beta) and/or Helicobacter infection. Helper T cell (Th) 1 and Th17 immune responses were inhibited by IFN-gamma through Fas induction and apoptosis in CD4 T cells. IFN-gamma also induced autophagy in gastric epithelial cells through increased expression of Beclin-1. Finally, in the gastric epithelium, IFN-gamma also inhibited IL-1beta- and Helicobacter-induced epithelial apoptosis, proliferation, and Dckl1(+) cell expansion. Taken together, our results suggest that IFN-gamma coordinately inhibits bacterial infection and carcinogenesis in the gastric mucosa by suppressing putative gastric progenitor cell expansion and reducing epithelial cell apoptosis via induction of an autophagic program. Cancer Res; 71(12); 4247-59. (c)2011 AACR. |
