title: Native and bone marrow-derived cell mosaicism in gastric carcinoma in H. pylori-infected p27-deficient mice.
abstract: OBJECTIVE
  Chronic Helicobacter pylori (H. pylori) infection promotes non-cardia gastric cancer. Some mouse models suggest that bone marrow derived cells (BMDC) contribute to Helicobacter-associated gastric carcinogenesis. We determined whether this increased susceptibility to Helicobacter-induced gastric carcinogenesis of p27-deficient mice is dependent upon their p27-null BMDC or their p27-null gastric epithelial cells.
  
  
  METHODS
  Female mice (recipients) were irradiated and transplanted with BMDC from male donors. Wild type (WT) mice in group 1 (control) received BMDC from male GFP-transgenic mice. Female WT and p27 KO mice were engrafted with male p27KO mice BMDC (Group 2) or GFP-transgenic WT BMDC (Group 3). Recipients were infected with H. pylori SS1 for one year.
  
  
  RESULTS
  Mice lacking p27 in either the BM pool or gastric epithelium developed significantly more advanced gastric pathology, including high-grade dysplasia. Co-staining of donor BMDC in dysplastic gastric glands was confirmed by immunofluorescence. Gastric expression of IL-1 beta protein was reduced in groups 2 and 3 (p < 0.05 vs control) whereas expression of IFN-γ and chemokines MIP-1 beta, MIG, IP-10 and RANTES in group 2 were significantly higher than group 3.
  
  
  CONCLUSIONS
  Both bone marrow-derived and gastric epithelial cells contribute to the increased gastric cancer susceptibility of p27-deficient H. pylori-infected mice.
authors.affiliation: Division of Gastroenterology, Rhode Island Hospital, Warren Alpert Medical School of Brown University, Providence, RI, USA.
authors.forename: Songhua
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Division of Gastroenterology, Rhode Island Hospital, Warren Alpert Medical School of Brown University, Providence, RI, USA.
authors.forename: Woojin
authors.initials: W
authors.lastname: Kim
authors.affiliation: Division of Gastroenterology, Rhode Island Hospital, Warren Alpert Medical School of Brown University, Providence, RI, USA.
authors.forename: Tu T
authors.initials: TT
authors.lastname: Pham
authors.affiliation: Department of Biomedical Sciences, Tufts Cummings School of Veterinary Medicine, Tufts University, North Grafton, MA, USA.
authors.forename: Arlin B
authors.initials: AB
authors.lastname: Rogers
authors.affiliation: Department of Medicine and Cancer Biology, Division of Gastroenterology, University of Massachusetts Medical School, Worcester, MA, USA.
authors.forename: Jean Marie
authors.initials: JM
authors.lastname: Houghton
authors.affiliation: Division of Gastroenterology, Rhode Island Hospital, Warren Alpert Medical School of Brown University, Providence, RI, USA.
authors.forename: Steven F
authors.initials: SF
authors.lastname: Moss
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000378:metabolism* / Q000382:microbiology; D016026:Bone Marrow Transplantation / Q000379:methods; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000172:deficiency* / Q000235:genetics; D016207:Cytokines / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D016481:Helicobacter Infections / Q000378:metabolism* / Q000382:microbiology; D016480:Helicobacter pylori / Q000502:physiology; D006801:Humans; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009030:Mosaicism; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000382:microbiology
chemical_list: C493961:Cdkn1b protein, mouse; D016207:Cytokines; D050760:Cyclin-Dependent Kinase Inhibitor p27
keywords: Helicobacter pylori; bone marrow transplantation; cytokines; gastric cancer; inflammation