We previously showed that antral gastric tumors develop in gastrin-deficient (Gas-/-) mice. Therefore Gas-/-mice were studied sequentially over 12 months to identify molecular mechanisms underlying gastric transformation. Fundic atrophy developed by 9 months in Gas-/- mice. Antral mucosal hyperplasia developed coincident with the focal loss of TFF1 and Muc5AC. Microarray analysis of 12 month Gas-/- tumors revealed an increase in follistatin, an activin/BMP antagonist. We found that elevated follistatin expression occurred in the proliferative neck zone of hyperplastic antrums, in antral tumors of Gas-/- mice, and also in human gastric cancers. Follistatin induced cyclin D1 and the trefoil factors TFF1 and TFF2 in a gastric cancer cell line. We concluded that antral hyperplasia in Gas-/- mice involves amplification of mucous cell lineages due to follistatin, suggesting its role in the development of antral gastric tumors.
|Original language||English (US)|
|Number of pages||5|
|Journal||Biochemical and Biophysical Research Communications|
|State||Published - Nov 21 2008|
Bibliographical noteFunding Information:
This work was supported in part by Public Health Service Grant R01-DK61410 to J.L.M. and the Michigan Gastrointestinal Peptide Research Center P30-DK34933.
- Atrophic gastritis
- Gastric cancer
- Intestinal metaplasia
- Mucous neck cell