| First Author | Katz JP | Year | 2005 |
| Journal | Gastroenterology | Volume | 128 |
| Issue | 4 | Pages | 935-45 |
| PubMed ID | 15825076 | Mgi Jnum | J:97350 |
| Mgi Id | MGI:3575322 | Doi | 10.1053/j.gastro.2005.02.022 |
| Citation | Katz JP, et al. (2005) Loss of Klf4 in mice causes altered proliferation and differentiation and precancerous changes in the adult stomach. Gastroenterology 128(4):935-45 |
| abstractText | BACKGROUND & AIMS: The epithelial zinc-finger transcription factor Klf4 (formerly GKLF) regulates cellular proliferation and differentiation in vitro. Klf4 null mice die by postnatal day 1 and show changes in epithelial differentiation of skin and colon. METHODS: We used tissue-specific gene ablation to generate mice lacking Klf4 in their gastric epithelia. Klf4 mutant mice and controls were killed for histology, immunohistochemistry, quantitative real-time polymerase chain reaction (qPCR), and serum gastrin levels. Klf4 messenger RNA (mRNA) levels were analyzed in Foxa3-Cdx2 transgenic mice and controls. Human gastric cancers and matched normal tissue were used for qPCR and immunohistochemistry for KLF4. RESULTS: Klf4 mutant mice survive to adulthood and show increased proliferation and altered differentiation of their gastric epithelia. Klf4 mutants also display aberrant expression of acidic mucins and TFF2/SP-positive cells, findings characteristic of premalignant conditions, but no inflammation, intestinal metaplasia, dysplasia, or cancer up to 1 year of age. Expression of KLF4 is nearly absent in human gastric cancer, suggesting that failure to activate KLF4 during normal cellular differentiation may be a common feature of gastric cancers. p21 WAF1/CIP1 is an in vivo target of Klf4, but Klf4 is not a mediator of Cdx2. CONCLUSIONS: Loss of a single genetic factor, Klf4, leads to dramatic changes in the gastric epithelia of mice, and Klf4 is part of a regulatory pathway involving p21 WAF1/CIP1 but not Cdx2. Thus, Klf4 is critical for normal gastric epithelial homeostasis. |
