Helicobacter pylori evolution during progression from chronic atrophic gastritis to gastric cancer and its impact on gastric stem cells
- *Center for Genome Sciences, Washington University School of Medicine, St. Louis, MO 63108;
- †Department of Anatomy, Faculty of Medicine and Health Sciences, United Arab Emirates University, Al-Ain 17666, United Arab Emirates;
- ‡Department of Microbiology, Tumor, and Cell Biology, Karolinska Institute, 171 77 Stockholm, Sweden; and
- §Swedish Institute for Infectious Disease Control, 171 82 Solna, Sweden
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Contributed by Jeffrey I. Gordon, January 22, 2008 (received for review December 5, 2007)
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Fig. 1.Association of H. pylori with gastric epithelial progenitors. In this multilabel immunohistochemical analysis, bacteria (red) are seen in association with BrdU-labeled GEPs (green) in the epithelium of a gnotobiotic transgenic tox176 mouse colonized with the cancer-associated Kx2 isolate. The epithelial marker, E-cadherin, appears white, and nuclei are stained blue with DAPI. Dashed lines indicate Kx2-associated progenitor cells that were targeted by n-LCM for transcriptional assays (see SI Text for details). (Scale bar: 25 μm.)
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Fig. 2.Flow-chart showing the approach used to define isolate-specific and progenitor-specific mGEP transcriptional responses to infection with the Kx1 and Kx2 isolates.
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Fig. 3.Kx2-associated up-regulation of antizyme inhibitor 1 expression in gastric epithelial progenitors in vitro and in vivo. (A) Mouse GeneChip analysis showing mGEP-specific up-regulation of antizyme inhibitor 1 (Azin1) after infection with the cancer-associated Kx2 strain. Three independent experiments for each condition were performed. Numbers at the bottom indicate standard deviations above (red) or below (green) the mean level of expression (black) of the Azin1 gene. (B) qRT-PCR of mGEP responses to Kx1 and Kx2 infection. *, P < 0.05; **, P < 0.01 in a two-sample two-tailed Student's t test with three biological replicates per condition for each mGEP transcript. (C) Up-regulation of Azin1 and Odc1 in gastric epithelial progenitor cells recovered by n-LCM from a tox176 mouse that had been colonized for 6 months with the Kx2 strain (mean values ± 1 SD for two to three technical replicates are plotted). *, P < 0.05.
Footnotes
- ¶To whom correspondence should be addressed. E-mail: jgordon{at}wustl.edu
- © 2008 by The National Academy of Sciences of the USA
