ArticleGastroenterology2009
Epidermal growth factor receptor activation protects gastric epithelial cells from Helicobacter pylori-induced apoptosis.
Article in Gastroenterology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers, 1 of them a synthesis that pooled it.
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Who cites it
63 citing papers in PubMed, 1 synthesis or guideline pooled it, 114 citations in OpenAlex.
- Helicobacter pylori and gastritis: the role of extracellular matrix metalloproteases, their inhibitors, and the disintegrins and metalloproteases--a systematic literature review.Digestive diseases and sciences · 2013Pooled it
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- The composition and roles of gastric stem cells in epithelial homeostasis, regeneration, and tumorigenesis.Cellular oncology (Dordrecht, Netherlands) · 2023Review
- Proteolytic Landscapes in Gastric Pathology and Cancerogenesis.International journal of molecular sciences · 2022Review
- The evolution of regulated cell death pathways in animals and their evasion by pathogens.Physiological reviews · 2022Review
- Relationships among microbiota, gastric cancer, and immunotherapy.Frontiers in microbiology · 2022Review
- Histone H3 deacetylation promotes host cell viability for efficient infection by Listeria monocytogenes.PLoS pathogens · 2021Article
- Bartonella henselae Persistence within Mesenchymal Stromal Cells Enhances Endothelial Cell Activation and Infectibility That Amplifies the Angiogenic Process.Infection and immunity · 2021Article
- Effects of a Potential Probiotic Strain Lactobacillus gasseri ATCC 33323 on Helicobacter pylori-Induced Inflammatory Response and Gene Expression in Coinfected Gastric Epithelial Cells.Probiotics and antimicrobial proteins · 2021Article
- A novel method for isolation and culture of primary swine gastric epithelial cells.BMC molecular and cell biology · 2021Article
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- Di-n-butyl phthalate epigenetically induces reproductive toxicity via the PTEN/AKT pathway.Cell death & disease · 2019Article
- The Possible Role ofFrontiers in oncology · 2019Review
- Resolution of Gastric Cancer-Promoting Inflammation: A Novel Strategy for Anti-cancer Therapy.Current topics in microbiology and immunology · 2019Review
- Article
3 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
BACKGROUND &
aimsHelicobacter pylori infection disrupts the balance between gastric epithelial cell proliferation and apoptosis, which is likely to lower the threshold for the development of gastric adenocarcinoma. H pylori infection is associated with epidermal growth factor (EGF) receptor (EGFR) activation through metalloproteinase-dependent release of EGFR ligands in gastric epithelial cells. Because EGFR signaling regulates cell survival, we investigated whether activation of EGFR following H pylori infection promotes gastric epithelial survival.
methodsMouse conditionally immortalized stomach epithelial cells (ImSt) and a human gastric epithelial cell line, AGS cells, as well as wild-type and kinase-defective EGFR (EGFRwa2) mice, were infected with the H pylori cag+ strain 7.13. Apoptosis, caspase activity, EGFR activation (phosphorylation), and EGFR downstream targets were analyzed.
resultsInhibiting EGFR kinase activity or decreasing EGFR expression significantly increased H pylori-induced apoptosis in ImSt. Blocking H pylori-induced EGFR activation with a heparin-binding (HB)-EGF neutralizing antibody or abrogating a disintegrin and matrix metalloproteinase-17 (ADAM-17) expression increased apoptosis of H pylori-infected AGS and ImSt, respectively. Conversely, pretreatment of ImSt with HB-EGF completely blocked H pylori-induced apoptosis. H pylori infection stimulated gastric epithelial cell apoptosis in EGFRwa2 but not in wild-type mice. Furthermore, H pylori-induced EGFR phosphorylation stimulated phosphotidylinositol-3'-kinase-dependent activation of the antiapoptotic factor Akt, increased expression of the antiapoptotic factor Bcl-2, and decreased expression of the proapoptotic factor Bax.
conclusionsEGFR activation by H pylori infection has an antiapoptotic effect in gastric epithelial cells that appears to involve Akt signaling and Bcl family members. These findings provide important insights into the mechanisms of H pylori-associated tumorigenesis.
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