Induction of follistatin precedes gastric transformation in gastrin deficient mice.
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.
Kang
Weiqun
W
Department of Internal Medicine, University of Michigan, 109 Zina Pitcher Place, BSRB 2051, Ann Arbor, MI 48109-2200, USA.
Saqui-Salces
Milena
M
Zavros
Yana
Y
Merchant
Juanita L
JL
D000818:Animals; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D019938:Cyclin D1 / Q000096:biosynthesis; D038681:Follistatin / Q000096:biosynthesis*; D005753:Gastric Mucosa / Q000378:metabolism / Q000473:pathology; D005755:Gastrins / Q000235:genetics*; D006965:Hyperplasia; D051379:Mice; D018345:Mice, Knockout; D009077:Mucins / Q000096:biosynthesis; D009124:Muscle Proteins / Q000096:biosynthesis; D010455:Peptides / Q000378:metabolism; D011706:Pyloric Antrum / Q000378:metabolism / Q000473:pathology*; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D000071163:Trefoil Factor-1; D000071164:Trefoil Factor-2
D038681:Follistatin; D005755:Gastrins; D009077:Mucins; D009124:Muscle Proteins; D010455:Peptides; C000604007:TFF2 protein, human; C481546:TFF2 protein, mouse; C472724:Tff1 protein, mouse; D000071163:Trefoil Factor-1; D000071164:Trefoil Factor-2; D019938:Cyclin D1