ArticleGastroenterology2009
Zinc replenishment reverses overexpression of the proinflammatory mediator S100A8 and esophageal preneoplasia in the rat.
Article in Gastroenterology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 45 citations in OpenAlex.
- Thr3/Ser90 phosphorylation-stabilized S100A8 regulates cholesterol metabolism in glioblastoma stem cells.Oncogene · 2026Article
- Zinc treatment reverses and anti-Zn-regulated miRs suppress esophageal carcinomas in vivo.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Upper Gastrointestinal Cancer and Liver Cirrhosis.Cancers · 2022Review
- Effects of dietary zinc deficiency on esophageal squamous cell proliferation and the mechanisms involved.World journal of gastrointestinal oncology · 2021Article
- Inhibition of the lncRNA Coded within Transglutaminase 2 Gene Impacts Several Relevant Networks in MCF-7 Breast Cancer Cells.Non-coding RNA · 2021Article
- Role and Mechanisms of RAGE-Ligand Complexes and RAGE-Inhibitors in Cancer Progression.International journal of molecular sciences · 2020Review
- Abrogation of esophageal carcinoma development in miR-31 knockout rats.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Calprotectin and the Initiation and Progression of Head and Neck Cancer.Journal of dental research · 2018Review
- Protein S100-A8: A potential metastasis-associated protein for breast cancer determined via iTRAQ quantitative proteomic and clinicopathological analysis.Oncology letters · 2018Article
- A nutrigenetic approach for investigating the chemopreventive effects of black raspberries during the development of preneoplastic esophagi in rats.Journal of berry research · 2018Article
- COX-2 metabolic products, the prostaglandin IOncotarget · 2017Article
- Research progress on the relationship between zinc deficiency, related microRNAs, and esophageal carcinoma.Thoracic cancer · 2017Review
- Article
- MicroRNA dysregulation and esophageal cancer development depend on the extent of zinc dietary deficiency.Oncotarget · 2016Article
- Repression of Esophageal Neoplasia and Inflammatory Signaling by Anti-miR-31 Delivery In Vivo.Journal of the National Cancer Institute · 2015Article
- Molecular mechanisms of ethanol-associated oro-esophageal squamous cell carcinoma.Cancer letters · 2015Review
- Article
- Overexpression of human β-defensin 2 promotes growth and invasion during esophageal carcinogenesis.Oncotarget · 2014Article
- Zinc and gastrointestinal disease.World journal of gastrointestinal pathophysiology · 2014Review
- Systematic review of zinc biomarkers and esophageal cancer risk.Middle East journal of digestive diseases · 2014Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
BACKGROUND &
aimsZinc deficiency is implicated in the pathogenesis of human esophageal cancer. In the rat esophagus, it induces cell proliferation, modulates genetic expression, and enhances carcinogenesis. Zinc-replenishment reverses proliferation and inhibits carcinogenesis. The zinc-deficient rat model allows the identification of biological differences affected by zinc during early esophageal carcinogenesis.
methodsWe evaluated gene expression profiles of esophageal epithelia from zinc-deficient and replenished rats vs zinc-sufficient rats using microarray analysis. We characterized the role of the top-up-regulated gene S100A8 in esophageal hyperplasia/reversal and in chemically induced esophageal carcinogenesis in zinc-modulated animals by immunohistochemistry and real-time quantitative polymerase chain reaction.
resultsThe hyperplastic-deficient esophagus has a distinct expression signature with the proinflammation genes S100 calcium binding protein A8 (S100A8) and A9 (S100A9) up-regulated 57-fold and 5-fold, respectively. Zinc replenishment rapidly restored to control levels the expression of S100A8/A9 and 27 other genes and reversed the hyperplastic phenotype. With its receptor for advanced glycation end products (RAGE), colocalization and overexpression of S100A8 protein occurred in the deficient esophagus that overexpressed nuclear factor kappaBeta p65 and cyclooxygenase-2 (COX-2) protein. Zinc replenishment, but not a COX-2 inhibitor, reduced the overexpression of these 4 proteins. Additionally, esophageal S100A8/A9 messenger RNA levels were associated directly with the diverse tumorigenic outcome in zinc-deficient and zinc-replenished rats.
conclusionsIn vivo zinc regulates S100A8 expression and modulates the link between S100A8-RAGE interaction and downstream nuclear factor kappaBeta/COX-2 signaling. The finding that zinc regulates an inflammatory pathway in esophageal carcinogenesis may lead to prevention and therapy for this cancer.
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