ArticleCancer research2004
Epidermal growth factor receptor regulates aberrant expression of insulin-like growth factor-binding protein 3.
Article in Cancer research, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers, 2 of them syntheses that pooled it.
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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
52 citing papers in PubMed, 2 syntheses or guidelines pooled it, 89 citations in OpenAlex.
- The low IGFBP-3 level is associated with esophageal cancer patients: a meta-analysis.World journal of surgical oncology · 2016Pooled it
- Pooled it
- AKT/mTOR as a targetable hub to overcome multimodal resistance to EGFR inhibitors in oesophageal squamous cell carcinoma.British journal of cancer · 2025Article
- The role of IGFBP-3 in tumor development and progression: enlightenment for diagnosis and treatment.Medical oncology (Northwood, London, England) · 2024Review
- Article
- Autocrine IGF-II-Associated Cancers: From a Rare Paraneoplastic Event to a Hallmark in Malignancy.Biomedicines · 2023Article
- Secretome analysis reveals reduced expression of COL4A2 in hypoxic cancer-associated fibroblasts with a tumor-promoting function in gastric cancer.Journal of cancer research and clinical oncology · 2023Article
- IGFBP3 induced by the TGF-β/EGFRvIII transactivation contributes to the malignant phenotype of glioblastoma.iScience · 2023Article
- Article
- Amniotic fluid stem cell administration can prevent epithelial injury from necrotizing enterocolitis.Pediatric research · 2022Article
- Bioinformatic Reconstruction and Analysis of Gene Networks Related to Glucose Variability in Diabetes and Its Complications.International journal of molecular sciences · 2020Article
- Protective effects of Alda-1, an ALDH2 activator, on alcohol-derived DNA damage in the esophagus of human ALDH2*2 (Glu504Lys) knock-in mice.Carcinogenesis · 2020Article
- Epigenetic silencing of IGFBPL1 promotes esophageal cancer growth by activating PI3K-AKT signaling.Clinical epigenetics · 2020Article
- Cyclin G2 Inhibits Oral Squamous Cell Carcinoma Growth and Metastasis by Binding to IGFBP3 and Regulating the FAK-SRC-STAT Signaling Pathway.Frontiers in oncology · 2020Article
- Up-regulation of Insulin-like Growth Factor Binding Protein-3 Is Associated with Brain Metastasis in Lung Adenocarcinoma.Molecules and cells · 2019Article
- Laparoscopic fluorescence image-guided photothermal therapy enhances cancer diagnosis and treatment.Nanotheranostics · 2019Article
- DpdtbA-Induced Growth Inhibition in Human Esophageal Cancer Cells Involved Inactivation of the p53/EGFR/AKT Pathway.Oxidative medicine and cellular longevity · 2019Article
- Insulin-like growth factor-1, IGF binding protein-3, and the risk of esophageal cancer in a nested case-control study.World journal of gastroenterology · 2017Article
- Low expression levels of insulin-like growth factor binding protein-3 are correlated with poor prognosis for patients with hepatocellular carcinoma.Oncology letters · 2017Article
- Successes and Failures of Combined Modalities in Upper Gastrointestinal Malignancies: New Directions.Seminars in radiation oncology · 2016Review
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 3 countries.
Funding
Abstract
Epidermal growth factor receptor (EGFR) is frequently overexpressed in esophageal carcinoma and its precursor lesions. To gain insights into how EGFR overexpression affects cellular functions in primary human esophageal cells, we performed gene expression profiling and identified insulin-like growth factor-binding protein (IGFBP)-3 as the most up-regulated gene. IGFBP-3 regulates cell proliferation through both insulin-like growth factor-dependent and independent mechanisms. We found that IGFBP-3 mRNA and protein expression was increased in EGFR-overexpressing primary and immortalized human esophageal cells. IGFBP-3 was also up-regulated in EGFR-overexpressing cells in organotypic culture and in EGFR transgenic mice. Furthermore, IGFBP-3 mRNA was overexpressed in 80% of primary esophageal squamous cell carcinomas and 60% of primary esophageal adenocarcinomas. Concomitant up-regulation of EGFR and IGFBP-3 was observed in 60% of primary esophageal squamous cell carcinomas. Immunohistochemistry revealed cytoplasmic localization of IGFBP-3 in the preponderance of preneoplastic and neoplastic esophageal lesions. IGFBP-3 was also overexpressed in esophageal cancer cell lines at both mRNA (60%) and protein (40%) levels. IGFBP-3 secreted by cancer cells was capable of binding to insulin-like growth factor I. Functionally, epidermal growth factor appeared to regulate IGFBP-3 expression in esophageal cancer cell lines. Finally, suppression of IGFBP-3 by small interfering RNA augmented cell proliferation, suggesting that IGFBP-3 may inhibit tumor cell proliferation as a negative feedback mechanism. In aggregate, we have identified for the first time that IGFBP-3 is an aberrantly regulated gene through the EGFR signaling pathway and it may modulate EGFR effects during carcinogenesis.
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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.