ArticleArchives of toxicology2014
Arsenic-induced cancer cell phenotype in human breast epithelia is estrogen receptor-independent but involves aromatase activation.
Article in Archives of toxicology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 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
27 citing papers in PubMed, 2 syntheses or guidelines pooled it, 67 citations in OpenAlex.
- Relationship Between Arsenic in Biological Media and Breast Cancer: A Systematic Review and Meta-Analysis.Biological trace element research · 2025Pooled it
- Breast Cancer and Arsenic Anticancer Effects: Systematic Review of the Experimental Data fromBioMed research international · 2022Pooled it
- Exploring the Influence of Chemical Exposures in Breast Cancer Disparities: High-Throughput Transcriptomic Analysis in Normal Breast Cells from Diverse Donors.bioRxiv : the preprint server for biology · 2026Article
- Long-Term Effect of Early-Life Arsenic Exposure on Morning Plasma Cortisol in Adults from Antofagasta, Chile.medRxiv : the preprint server for health sciences · 2025Article
- Endocrine-disrupting chemicals as prostate carcinogens.Nature reviews. Urology · 2025Review
- The Role of Heavy Metals in the Biology of Female Cancers.International journal of molecular sciences · 2025Review
- Heavy-metal associated breast cancer and colorectal cancer hot spots and their demographic and socioeconomic characteristics.Cancer causes & control : CCC · 2024Article
- Elevated aerobic glycolysis driven by p62-mTOR axis promotes arsenic-induced oncogenic phenotypes in human mammary epithelial cells.Archives of toxicology · 2024Article
- The carcinogenic capacity of arsenic in normal epithelial breast cells and double-positive breast cancer cells.Medicine and pharmacy reports · 2024Article
- Nanoplastics and Arsenic Co-Exposures Exacerbate Oncogenic Biomarkers under an In Vitro Long-Term Exposure Scenario.International journal of molecular sciences · 2022Article
- Epigenetics and environment in breast cancer: New paradigms for anti-cancer therapies.Frontiers in oncology · 2022Review
- An approach to classifying occupational exposures to endocrine disrupting chemicals by sex hormone function using an expert judgment process.Journal of exposure science & environmental epidemiology · 2021Review
- Nutrition, one-carbon metabolism and arsenic methylation.Toxicology · 2021Review
- Inorganic arsenic promotes luminal to basal transition and metastasis of breast cancer.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020Article
- Assessment of YAP gene polymorphisms and arsenic interaction in Mexican women with breast cancer.Journal of applied toxicology : JAT · 2020Article
- Toxic Effects of Chronic Exposure to High-Fat Diet and Arsenic on the Reproductive System of the Male Mouse.Journal of family & reproductive health · 2019Article
- Environmental exposures, stem cells, and cancer.Pharmacology & therapeutics · 2019Review
- Arsenic‑induced BRCA1 CpG promoter methylation is associated with the downregulation of ERα and resistance to tamoxifen in MCF7 breast cancer cells and mouse mammary tumor xenografts.International journal of oncology · 2019Article
- Nutritional Influences on One-Carbon Metabolism: Effects on Arsenic Methylation and Toxicity.Annual review of nutrition · 2018Review
- Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Accumulating data suggest arsenic may be an endocrine disruptor and tentatively linked to breast cancer by some studies. Therefore, we tested the effects of chronic inorganic arsenic exposure on the normal estrogen receptor (ER)-negative breast epithelial cell line, MCF-10A. Cells were chronically exposed to a low-level arsenite (500 nM) for up to 24 weeks. Markers of cancer cell phenotype and the expression of critical genes relevant to breast cancer or stem cells (SCs) were examined. After 24 weeks, chronic arsenic-exposed breast epithelial (CABE) cells showed increases in secreted MMP activity, colony formation, invasion, and proliferation rate, indicating an acquired cancer cell phenotype. These CABE cells presented with basal-like breast cancer characteristics, including ER-α, HER-2, and progesterone receptor negativity, and overexpression of K5 and p63. Putative CD44(+)/CD24(-/low) breast SCs were increased to 80 % over control in CABE cells. CABE cells also formed multilayer cell mounds, indicative of loss of contact inhibition. These mounds showed high levels of K5 and p63, indicating the potential presence of cancer stem cells (CSCs). Epithelial-to-mesenchymal transition occurred during arsenic exposure. Overexpression of aromatase, a key rate-limiting enzyme in estrogen synthesis, occurred with arsenic starting early on in exposure. Levels of 17β-estradiol increased in CABE cells and their conditioned medium. The aromatase inhibitor letrozole abolished arsenic-induced increases in 17β-estradiol production and reversed cancer cell phenotype. Thus, chronic arsenic exposure drives human breast epithelia into a cancer cell phenotype with an apparent overabundance of putative CSCs. Arsenic appears to transform breast epithelia through overexpression of aromatase, thereby activating oncogenic processes independent of ER.
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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.