ArticleGastroenterology2011
Inhibition of gastric carcinogenesis by the hormone gastrin is mediated by suppression of TFF1 epigenetic silencing.
Article in Gastroenterology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 83 papers, 1 of them a synthesis that pooled it.
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Who cites it
83 citing papers in PubMed, 1 synthesis or guideline pooled it, 126 citations in OpenAlex.
- Homeobox proteins are potential biomarkers and therapeutic targets in gastric cancer: a systematic review and meta-analysis.BMC cancer · 2020Pooled it
- Bad bugs mean business: gastric cancer is an intended consequence ofInfection and immunity · 2026Review
- Animal models and pathogenesis of gastric cancer: from premalignant conditions-to-metastasis.Cancer biology & medicine · 2026Review
- Characterization of Monomeric and Dimeric Forms of the Lectin TFF1 in the Human Vagina: Possible Role for the Innate Immune Defence.International journal of molecular sciences · 2026Article
- Conventional and Novel Approaches to Establishing Mouse Models of Gastric Cancer in the Past, Present, and Potential Post-H. Pylori Infection Era.Biological procedures online · 2026Review
- Somatostatin Effect on Growth Factors in Hepatocellular Carcinoma.Current issues in molecular biology · 2026Article
- Article
- Genetically engineered mouse models in gastric precancerous lesions research.World journal of gastrointestinal surgery · 2025Review
- Nerves at Play: The Peripheral Nervous System in Extracranial Malignancies.Cancer discovery · 2025Review
- Long-term memory in epithelia: transient IFNγ exposure drives stable repression of TFF1 in gastric epithelial cells via epigenetic changes.Frontiers in immunology · 2025Article
- Glucose homeostasis controls N-acetyltransferase 10-mediated ac4C modification of HK2 to drive gastric tumorigenesis.Theranostics · 2025Article
- Precancerous pathways to gastric cancer: a review of experimental animal models recapitulating the correa cascade.Frontiers in cell and developmental biology · 2025Review
- Modeling human gastric cancers in immunocompetent mice.Cancer biology & medicine · 2024Review
- Loss of ATOH1 in Pit Cell Drives Stemness and Progression of Gastric Adenocarcinoma by Activating AKT/mTOR Signaling through GAS1.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- The composition and roles of gastric stem cells in epithelial homeostasis, regeneration, and tumorigenesis.Cellular oncology (Dordrecht, Netherlands) · 2023Review
- Prognostic biomarkers and molecular pathways mediating Helicobacter pylori-induced gastric cancer: a network-biology approach.Genomics & informatics · 2023Article
- Non-Gastro hep advances · 2023Article
- Current trends and future prospects of drug repositioning in gastrointestinal oncology.Frontiers in pharmacology · 2023Review
- IFNγ-dependent silencing of TFF1 duringOpen biology · 2022Article
- The immune microenvironment in gastric adenocarcinoma.Nature reviews. Gastroenterology & hepatology · 2022Review
23 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
15 authors at 8 institutions in 5 countries.
Funding
Abstract
BACKGROUND &
aimsEpigenetic alterations have been correlated with field cancerization in human patients, but evidence from experimental models that specific epigenetic changes can initiate cancer has been lacking. Although hormones have been associated with cancer risk, the mechanisms have not been determined. The peptide hormone gastrin exerts a suppressive effect on antral gastric carcinogenesis.
methodsN-methyl-N-nitrosourea (MNU)-dependent gastric cancer was investigated in hypergastrinemic (INS-GAS), gastrin-deficient (GAS(-/-)), Tff1-deficient (Tff1(+/-)), and wild-type (WT) mice. Epigenetic alterations of the trefoil factor 1 (TFF1) tumor suppressor gene were evaluated in vitro and in vivo.
resultsHuman intestinal-type gastric cancers in the antrum exhibited progressive TFF1 repression and promoter hypermethylation. Mice treated with MNU exhibited a field defect characterized by widespread Tff1 repression associated with histone H3 lysine 9 methylation and H3 deacetylation at the Tff1 promoter in epithelial cells. In MNU-induced advanced cancers, DNA methylation at the Tff1 promoter was observed. Tumor induction and Tff1 repression were increased in MNU-treated mice by Helicobacter infection. Hypergastrinemia suppressed MNU-dependent tumor initiation and progression in a manner that correlated with gene silencing and epigenetic alterations of Tff1. In contrast, homozygous gastrin-deficient and heterozygous Tff1-deficient mice showed enhanced MNU-dependent field defects and cancer initiation compared with WT mice. In gastric cancer cells, gastrin stimulation partially reversed the epigenetic silencing in the TFF1 promoter.
conclusionsInitiation of antral gastric cancer is associated with progressive epigenetic silencing of TFF1, which can be suppressed by the hormone gastrin.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.