| First Author | Tetreault MP | Year | 2010 |
| Journal | Gastroenterology | Volume | 139 |
| Issue | 6 | Pages | 2124-2134.e9 |
| PubMed ID | 20816834 | Mgi Jnum | J:334764 |
| Mgi Id | MGI:7464176 | Doi | 10.1053/j.gastro.2010.08.048 |
| Citation | Tetreault MP, et al. (2010) Klf4 overexpression activates epithelial cytokines and inflammation-mediated esophageal squamous cell cancer in mice. Gastroenterology 139(6):2124-2134.e9 |
| abstractText | BACKGROUND & AIMS: Esophageal squamous cell cancer accounts for more than 90% of cases of esophageal cancers. Its pathogenesis involves chronic epithelial irritation, although the factors involved in the inflammatory process and the mechanisms of carcinogenesis are unknown. We sought to develop a mouse model of this cancer. METHODS: We used the ED-L2 promoter of Epstein-Barr virus to overexpress the transcriptional regulator Kruppel-like factor 4 (Klf4) in esophageal epithelia of mice; we used mouse primary esophageal keratinocytes to examine the mechanisms by which KLF4 induces cytokine production. RESULTS: KLF4 was an epithelial-specific mediator of inflammation; we developed a new mouse model of esophageal squamous dysplasia and inflammation-mediated squamous cell cancer. KLF4 activated a number of proinflammatory cytokines, including TNF-alpha, CXCL5, G-CSF and IL-1alpha, within keratinocytes in an NF-kappaB-dependent manner. KLF4 was not detected in proliferating or cancer cells, indicating a non-cell autonomous effect of KLF4 on proliferation and carcinogenesis. CONCLUSIONS: KLF4 has distinct functions in carcinogenesis; upregulation of Klf4 specifically in esophageal epithelial cells induces inflammation. This mouse model might be used to determine the molecular mechanisms of esophageal squamous cell cancer and inflammation-mediated carcinogenesis. |
