Induction of follistatin precedes gastric transformation in gastrin deficient mice

Biochem Biophys Res Commun. 2008 Nov 21;376(3):573-7. doi: 10.1016/j.bbrc.2008.09.031. Epub 2008 Sep 17.


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Transformation, Neoplastic / genetics*
  • Cell Transformation, Neoplastic / metabolism
  • Cell Transformation, Neoplastic / pathology*
  • Cyclin D1 / biosynthesis
  • Follistatin / biosynthesis*
  • Gastric Mucosa / metabolism
  • Gastric Mucosa / pathology
  • Gastrins / genetics*
  • Hyperplasia
  • Mice
  • Mice, Knockout
  • Mucins / biosynthesis
  • Muscle Proteins / biosynthesis
  • Peptides / metabolism
  • Pyloric Antrum / metabolism
  • Pyloric Antrum / pathology*
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / metabolism
  • Stomach Neoplasms / pathology*
  • Trefoil Factor-1
  • Trefoil Factor-2


  • Follistatin
  • Gastrins
  • Mucins
  • Muscle Proteins
  • Peptides
  • TFF2 protein, human
  • TFF2 protein, mouse
  • Tff1 protein, mouse
  • Trefoil Factor-1
  • Trefoil Factor-2
  • Cyclin D1