Bone morphogenetic protein signaling suppresses tumorigenesis at gastric epithelial transition zones in mice

Sylvia A. Bleuming, Xi C. He, Liudmila L. Kodach, James C. Hardwick, Frieda A. Koopman, Fiebo J. Ten Kate, Sander J H Van Deventer, Daniel W. Hommes, Maikel P. Peppelenbosch, G. Johan Offerhaus, Nheng Li, Gijs R. Van Den Brink

Research output: Contribution to journalArticlepeer-review

Abstract

Bone morphogenetic protein (BMP) signaling is known to suppress oncogenesis in the small and large intestine of mice and humans. We examined the role of Bmpr1a signaling in the stomach. On conditional inactivation of Bmpr1a, mice developed neoplastic lesions specificallyin the squamocolumnar and gastrointestinal transition zones. We hypothesized that the regulation of epithelial cell fate may be less well defined in these junctional zones than in the adjacent epithelium and found that the mucosa at the squamocolumnar junction in mice shows a lack of differentiated fundic gland cell types and that foveolar cells at the gastrointestinal junctional zone lack expression of the foveolar cell marker Muc5ac. Precursor cell proliferation in both transition zones was higher than in the surrounding epithelium. Our data show that BMP signaling through Bmpr1a suppresses tumorigenesis at gastric epithelial junctional zones that are distinct from the adjacent gastric epithelium in both cellular differentiation and proliferation.

Original languageEnglish (US)
Pages (from-to)8149-8155
Number of pages7
JournalCancer Research
Volume67
Issue number17
DOIs
StatePublished - Sep 1 2007
Externally publishedYes

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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