ArticleToxicological sciences : an official journal of the Society of Toxicology2009
Arsenic activates EGFR pathway signaling in the lung.
Article in Toxicological sciences : an official journal of the Society of Toxicology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 1 of them a synthesis that pooled it.
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29 citing papers in PubMed, 1 synthesis or guideline pooled it, 73 citations in OpenAlex.
- Toenails as a biomarker of exposure to arsenic: A review.Environmental research · 2021Pooled it
- Acute arsenic trioxide inhibits the cardiac transient outward KCurrent research in structural biology · 2026Article
- Memory effects of prior subculture may impact the quality of multiomic perturbation profiles.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
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- Epigenomic reprogramming in iAs-mediated carcinogenesis.Advances in pharmacology (San Diego, Calif.) · 2023Article
- Metal Exposures in Residents Living Near an Urban Oil Drilling Site in Los Angeles, California.Environmental science & technology · 2022Article
- Arsenic-induced epigenetic changes in cancer development.Seminars in cancer biology · 2021Review
- Chronic and acute arsenic exposure enhance EGFR expression via distinct molecular mechanisms.Toxicology in vitro : an international journal published in association with BIBRA · 2020Article
- Arsenic Stimulates Myoblast Mitochondrial Epidermal Growth Factor Receptor to Impair Myogenesis.Toxicological sciences : an official journal of the Society of Toxicology · 2020Article
- Molecular Mechanisms of Arsenic-Induced Disruption of DNA Repair.Chemical research in toxicology · 2020Review
- HB-EGF Activates the EGFR/HIF-1α Pathway to Induce Proliferation of Arsenic-Transformed Cells and Tumor Growth.Frontiers in oncology · 2020Article
- A candidate for lung cancer treatment: arsenic trioxide.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2019Review
- A review of arsenic exposure and lung cancer.Toxicology research · 2019Review
- PI3K/Akt/mTOR Signaling Pathway and the Biphasic Effect of Arsenic in Carcinogenesis.Molecular pharmacology · 2018Review
- iTRAQ-based quantitative proteomic analysis reveals important metabolic pathways for arsenic-induced liver fibrosis in rats.Scientific reports · 2018Article
- Oncogenomic disruptions in arsenic-induced carcinogenesis.Oncotarget · 2017Review
- Dual Roles of Oxidative Stress in Metal Carcinogenesis.Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer · 2017Review
- Chronic arsenic trioxide exposure leads to enhanced aggressiveness via Met oncogene addiction in cancer cells.Oncotarget · 2016Article
- Cadmium promotes the proliferation of triple-negative breast cancer cells through EGFR-mediated cell cycle regulation.Toxicology and applied pharmacology · 2015Article
- Arsenic Inhibits DNA Mismatch Repair by Promoting EGFR Expression and PCNA Phosphorylation.The Journal of biological chemistry · 2015Article
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4 authors at 2 institutions in 2 countries.
Funding
Abstract
Arsenic is an established lung carcinogen, however, the carcinogenic mechanisms are currently under investigation. Phosphorylation of the epidermal growth factor receptor (EGFR) has been reported with arsenic exposure in bladder cells. EGFR is a tyrosine kinase transmembrane receptor that regulates important processes in carcinogenesis, including cell survival, cell cycle progression, tumor invasion, and angiogenesis. We investigated the mechanisms of EGFR pathway activation by levels of arsenic relevant to human exposure scenarios both in vitro using cultured lung epithelial cells, and in lung tumors samples from New England Lung Cancer Study participants. Toenail arsenic levels were used as an internal biomarker of arsenic exposure. Our in vitro data suggest that arsenic increases levels of the EGFR ligand, heparin binding-EGF, and activate EGFR phosphorylation in the lung. Downstream of EGFR, arsenic exposure increased pERK and cyclin D1 levels. These effects were inhibited by treatment of cultured cells with the EGFR tyrosine kinase inhibitor, Tarceva (erlotinib). In a consecutive series of human lung tumor specimens, pEGFR protein levels were higher in subjects with elevated toenail arsenic levels compared to those with low exposure (odds ratio adjusted for other factors, OR 4.1 (95% confidence interval 1.1-15.6) (p = 0.04). These data suggest that arsenic exposure may stimulate EGFR pathway activation in the lung. Moreover, the tumors that arise in arsenic-exposed individuals also exhibit signs of EGFR pathway dysregulation. Further work is needed to assess the clinical utility of targeting the EGFR pathway in subgroups of lung cancer patients who have been exposed to elevated levels of arsenic.
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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.