Bone morphogenetic protein signaling suppresses tumorigenesis at gastric epithelial transition zones in mice.
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 specifically in 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.
Bleuming
Sylvia A
SA
Center for Experimental and Molecular Medicine, Academic Medical Center, Amsterdam, The Netherlands.
He
Xi C
XC
Kodach
Liudmila L
LL
Hardwick
James C
JC
Koopman
Frieda A
FA
Ten Kate
Fiebo J
FJ
van Deventer
Sander J H
SJ
Hommes
Daniel W
DW
Peppelenbosch
Maikel P
MP
Offerhaus
G Johan
GJ
Li
Linheng
L
van den Brink
Gijs R
GR
D000818:Animals; D052005:Bone Morphogenetic Protein Receptors, Type I / Q000235:genetics; D019485:Bone Morphogenetic Proteins / Q000502:physiology*; D002454:Cell Differentiation; D049109:Cell Proliferation; D018450:Disease Progression; D004847:Epithelial Cells / Q000473:pathology; D016147:Genes, Tumor Suppressor / Q000502:physiology; D007413:Intestinal Mucosa / Q000473:pathology*; D007414:Intestinal Neoplasms / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011706:Pyloric Antrum / Q000473:pathology*; D015398:Signal Transduction / Q000502:physiology; D013274:Stomach Neoplasms / Q000473:pathology*; D051176:beta Catenin / Q000378:metabolism