ArticleJournal of gastrointestinal cancer2012
Evidence for changes in RREB-1, ZIP3, and Zinc in the early development of pancreatic adenocarcinoma.
Article in Journal of gastrointestinal cancer, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
28 citing papers in PubMed, 39 citations in OpenAlex.
- Epigenomic characterization of locally advanced anal cancer: a radiation therapy oncology group 98-11 specimen study.Diseases of the colon and rectum · 2014Trial
- Molecular MRI of Dysregulated Zinc Secretion Detects Pancreatic Ductal Adenocarcinoma and Response to KRASG12D Inhibitor Treatment.Cancer research · 2025Article
- Zinc-Mediated Defenses Against Toxic Heavy Metals and Metalloids: Mechanisms, Immunomodulation, and Therapeutic Relevance.International journal of molecular sciences · 2025Review
- Dynamic Coupling of MAPK Signaling to the Guanine Nucleotide Exchange Factor GEF-H1.OncoTargets and therapy · 2025Review
- TGF-β signaling in health and disease.Cell · 2023Review
- Review
- Zinc: From Biological Functions to Therapeutic Potential.International journal of molecular sciences · 2023Review
- Construction of a prognostic model for colorectal adenocarcinoma based on Zn transport-related genes identified by single-cell sequencing and weighted co-expression network analysis.Frontiers in oncology · 2023Article
- Combination Cancer Treatment: Using Engineered DNAzyme Molecular Machines for Dynamic Inter- and Intracellular Regulation.Angewandte Chemie (International ed. in English) · 2022Article
- TGF-β in developmental and fibrogenic EMTs.Seminars in cancer biology · 2022Review
- p53 and Zinc: A Malleable Relationship.Frontiers in molecular biosciences · 2022Review
- Emerging roles of the solute carrier family in pancreatic cancer.Clinical and translational medicine · 2021Review
- Zinc dysregulation in cancers and its potential as a therapeutic target.Cancer biology & medicine · 2020Review
- Growth Modulatory Role of Zinc in Prostate Cancer and Application to Cancer Therapeutics.International journal of molecular sciences · 2020Review
- Transcription Factor RREB1: from Target Genes towards Biological Functions.International journal of biological sciences · 2020Review
- Article
- Role of ion channels in gastrointestinal cancer.World journal of gastroenterology · 2019Review
- Analysis the prognostic values of solute carrier (SLC) family 39 genes in gastric cancer.American journal of translational research · 2019Article
- Cadmium and Cadmium/Zinc Ratios and Tobacco-Related Morbidities.International journal of environmental research and public health · 2017Review
- Integrated Genomic Characterization of Pancreatic Ductal Adenocarcinoma.Cancer cell · 2017Article
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
Abstract
purposePancreatic adenocarcinoma is an untreatable cancer with a 5-year survival rate of about 6 % or less for the past 35 years. This lack of significant progress is largely due to the lack of elucidation and understanding of the factors involved in the development of this cancer. Recent studies identified and implicated zinc in the development and progression of pancreatic cancer. This study was conducted to establish the changes in zinc, ZIP3 zinc transporter, and Ras-responsive element-binding protein 1 (RREB-1) transcription factor as early events in the development of malignancy.
methodsIn situ relative zinc determination and immunohistochemical analysis of ZIP3 and RREB-1 were performed on archived human pancreatic tissue sections and tissue microarrays. Normal/benign versus adenocarcinoma pancreas was compared. Panc1 cells were employed to determine the influence of RREB-1 on ZIP3 expression.
resultsZinc levels of normal ductal and acinar epithelium were markedly and consistently decreased in adenocarcinoma. Pancreatic intraepithelial neoplasia (PanIN) lesions also exhibited a loss of zinc. ZIP3 and RREB-1 were also markedly downregulated. Initial results indicate that RREB-1 regulates ZIP3 expression.
conclusionsThese results corroborate the earlier report that zinc, ZIP3, and RREB-1 are markedly decreased in early stage adenocarcinoma. Additionally and most importantly, these changes occur in PanIN, which are thought to be precancerous lesions leading to ductal adenocarcinoma. These results support a concept that downregulation of RREB-1 causes downregulation of ZIP3, which results in decreased zinc in premalignant and carcinoma cells. The decrease in zinc is essential to remove its cytotoxic effects on malignant cells. This relationship constitutes a new concept of early genetic/metabolic events in the progressive transformation of normal cells to premalignant cells to malignant cells in the development of pancreatic cancer.
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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.