ArticleToxicological sciences : an official journal of the Society of Toxicology2014
AroER tri-screen is a biologically relevant assay for endocrine disrupting chemicals modulating the activity of aromatase and/or the estrogen receptor.
Article in Toxicological sciences : an official journal of the Society of Toxicology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 32 citations in OpenAlex.
- Use of Tox21 screening data to profile PFAS bioactivities on nuclear receptors, cellular stress pathways, and cytochrome p450 enzymes.Journal of hazardous materials · 2024Article
- New Evidence on BPA's Role in Adipose Tissue Development of Proinflammatory Processes and Its Relationship with Obesity.International journal of molecular sciences · 2023Review
- Review
- A Fluorometric CYP19A1 (Aromatase) Activity Assay in Live Cells.ChemMedChem · 2021Article
- A Gene Expression Biomarker Identifies Chemical Modulators of Estrogen Receptor α in an MCF-7 Microarray Compendium.Chemical research in toxicology · 2021Article
- Paroxetine-Overview of the Molecular Mechanisms of Action.International journal of molecular sciences · 2021Review
- Comparing Machine Learning Models for Aromatase (P450 19A1).Environmental science & technology · 2020Article
- Comparison of Machine Learning Models for the Androgen Receptor.Environmental science & technology · 2020Article
- Computational Study of Drugs Targeting Nuclear Receptors.Molecules (Basel, Switzerland) · 2020Article
- Towards a Treatment for Gulf War Illness: A Consensus Docking Approach.Military medicine · 2020Article
- Development of a prioritization method for chemical-mediated effects on steroidogenesis using an integrated statistical analysis of high-throughput H295R data.Regulatory toxicology and pharmacology : RTP · 2019Article
- Environmental exposures during windows of susceptibility for breast cancer: a framework for prevention research.Breast cancer research : BCR · 2019Review
- Molecular Mechanisms of Polybrominated Diphenyl Ethers (BDE-47, BDE-100, and BDE-153) in Human Breast Cancer Cells and Patient-Derived Xenografts.Toxicological sciences : an official journal of the Society of Toxicology · 2019Article
- Serum Testosterone Concentrations and Urinary Bisphenol A, Benzophenone-3, Triclosan, and Paraben Levels in Male and Female Children and Adolescents: NHANES 2011-2012.Environmental health perspectives · 2016Article
- Moving Toward Integrating Gene Expression Profiling Into High-Throughput Testing: A Gene Expression Biomarker Accurately Predicts Estrogen Receptor α Modulation in a Microarray Compendium.Toxicological sciences : an official journal of the Society of Toxicology · 2016Article
- Cell-Based High-Throughput Screening for Aromatase Inhibitors in the Tox21 10K Library.Toxicological sciences : an official journal of the Society of Toxicology · 2015Article
- AroER tri-screen™ is a novel functional assay to estimate both estrogenic and estrogen precursor activity of chemicals or biological specimens.Breast cancer research and treatment · 2015Article
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 1 country.
Funding
Abstract
Endocrine disrupting chemicals (EDCs) interfere with the biosynthesis, metabolism, and functions of steroid hormones, including estrogens and androgens. Aromatase enzyme converts androgen to estrogen. Thus, EDCs against aromatase significantly impact estrogen- and/or androgen-dependent functions, including the development of breast cancer. The current study aimed to develop a biologically relevant cell-based high-throughput screening assay to identify EDCs that act as aromatase inhibitors (AIs), estrogen receptor (ER) agonists, and/or ER antagonists. The AroER tri-screen assay was developed by stable transfection of ER-positive, aromatase-expressing MCF-7 breast cancer cells with an estrogen responsive element (ERE) driven luciferase reporter plasmid. The AroER tri-screen can identify: estrogenic EDCs, which increase luciferase signal without 17β-estradiol (E2); anti-estrogenic EDCs, which inhibit the E2-induced luciferase signal; and AI-like EDCs, which suppress a testosterone-induced luciferase signal. The assay was first optimized in a 96-well plate format and then miniaturized into a 1536-well plate format. The AroER tri-screen was demonstrated to be suitable for high-throughput screening in the 1536-well plate format, with a 6.9-fold signal-to-background ratio, a 5.4% coefficient of variation, and a screening window coefficient (Z-factor) of 0.78. The assay suggested that bisphenol A (BPA) functions mainly as an ER agonist. Results from screening the 446 drugs in the National Institutes of Health Clinical Collection revealed 106 compounds that modulated ER and/or aromatase activities. Among these, two AIs (bifonazole and oxiconazole) and one ER agonist (paroxetine) were confirmed through alternative aromatase and ER activity assays. These findings indicate that AroER tri-screen is a useful high-throughput screening system for identifying ER ligands and aromatase-inhibiting chemicals.
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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.