Metaplasia in the Stomach—Precursor of Gastric Cancer?
Hypertrophic gastric mucosa in transgenic miceoverexpressing transforming growth factor (TGF)-alphashowed mucosal cellular hyperplasia with dysplasia,suppression of gastric acid secretion, and chief and parietal cell depletion. In order toclarify the effects of TGF-alpha on the gastric mucosa,we analyzed the stomach of TGF-alpha transgenic mice bymucin histochemical staining and immunohistochemical analysis of TGF-alpha. In transgenic mice,especially those older than 3 months, the fundic glandwas notably atrophic but the total mucosa was thickened.The mucous neck cells were hypersecretory and associated with abnormal sulfation. Mucosal hyperplasiawas caused by proliferation of surface epithelial cells,associated with formation of intracytoplasmic lumina.The hyperplastic foveolar cells revealed production of a high amount of sialomucin. In addition,the involved stomach regionally revealed collagenousfibrosis in the submucosal layer. The wide distributionof TGF-alpha in the hyperplastic foveolar cells was in sharp contrast to negative expression inthe foveolar cells in the control mice. These findingsdemonstrated the various regulatory functions ofTGF-alpha in mucin production, fibrogenesis, and neck cell proliferation in the stomach.