Evidence map›Paper›PMID 29329451›Full record

ArticleToxicological sciences : an official journal of the Society of Toxicology2018

Epidermal Growth Factor Receptor Signaling Disruption by Endocrine and Metabolic Disrupting Chemicals.

Josiah E Hardesty, Laila Al-Eryani, Banrida Wahlang, K Cameron Falkner, Hongxue Shi, Jian Jin, Brad J Vivace, Brian P Ceresa, Russell A Prough, Matthew C Cave

Open access · bronzeAbstract read
In one paragraph

Article in Toxicological sciences : an official journal of the Society of Toxicology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.

0numbers the graph read from it
0cells of the map it votes in
38citing papers in PubMed
5.6field-weighted citation impact, top 4% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

38 citing papers in PubMed, 53 citations in OpenAlex.

  1. Review
  2. Review
  3. Epidermal growth factor receptor in placental health and disease: pathways, dysfunction, and chemical disruption.Toxicological sciences : an official journal of the Society of Toxicology · 2025
    Review
  4. Article
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  9. Sex-specific effects of acute chlordane exposure in the context of steatotic liver disease, energy metabolism and endocrine disruption.Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association · 2023
    Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 1 institution in 1 country.

Josiah E HardestyDepartment of Biochemistry and Molecular Genetics.
Laila Al-EryaniDepartment of Pharmacology and Toxicology.
Banrida WahlangDivision of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Louisville School of Medicine, Louisville, Kentucky 40202.
K Cameron FalknerDivision of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Louisville School of Medicine, Louisville, Kentucky 40202.
Hongxue ShiDepartment of Pharmacology and Toxicology.
Jian JinDepartment of Pharmacology and Toxicology.
Brad J VivaceDivision of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Louisville School of Medicine, Louisville, Kentucky 40202.
Brian P CeresaDepartment of Pharmacology and Toxicology.
Russell A ProughDepartment of Biochemistry and Molecular Genetics.
Matthew C CaveDepartment of Biochemistry and Molecular Genetics.
University of Louisville · US

Funding

Role of oxidized linoleic acid metabolites in the pathogenesis of alcoholic liver diseaseP20GM113226 · NIGMS · UNIVERSITY OF LOUISVILLE · PI BARVE, SHIRISH S · 2016 to 2025
$24.1M
Superfund Training CoreP42ES023716 · NIEHS · UNIVERSITY OF LOUISVILLE · PI SRIVASTAVA, SANJAY · 2017 to 2025
$18.1M
The Role of Nutrition in the Development/Progression of Alcohol-Induced Organ InjuryP50AA024337 · NIAAA · UNIVERSITY OF LOUISVILLE · PI CRAIG J. MCCLAIN · 2016 to 2026
$17.9M
Environmental Liver DiseaseR35ES028373 · NIEHS · UNIVERSITY OF LOUISVILLE · PI CAVE, MATTHEW C · 2017 to 2024
$4.0M
PCBs worsen obesity/metabolic syndrome through 'toxic metabolic endotoxemia'R01ES021375 · NIEHS · UNIVERSITY OF LOUISVILLE · PI CAVE, MATTHEW C · 2012 to 2016
$1.7M
Summer Environmental Health Sciences Training ProgramT35ES014559 · NIEHS · UNIVERSITY OF LOUISVILLE · PI Matthew C Cave, Daniel Joseph Conklin · 2006 to 2026
$751k
Identifying novel c-Cbl antagonists to promote corneal epithelial regenerationR21EY027032 · NEI · UNIVERSITY OF LOUISVILLE · PI CERESA, BRIAN P. · 2016 to 2017
$424k
Polychlorinated biphenyls act through EGFR to worsen NAFLDF31ES028982 · NIEHS · UNIVERSITY OF LOUISVILLE · PI HARDESTY, JOSIAH E · 2017 to 2018
$43k
NEI NIH HHS R21 EY027032NIAAA NIH HHS P50 AA024337NIEHS NIH HHS F31 ES028982NIEHS NIH HHS P42 ES023716NIEHS NIH HHS R01 ES021375NIEHS NIH HHS R35 ES028373NIEHS NIH HHS T35 ES014559NIGMS NIH HHS P20 GM113226
6 · The paper itself

Abstract

The purpose of this study is to identify an environmentally relevant shared receptor target for endocrine and metabolism disrupting chemical pollutants. A feature of the tested chemicals was that they induced Cyp2b10 in vivo implicating activation of the constitutive androstane receptor (CAR). Recent studies suggest that these compounds could be indirect CAR activators via epidermal growth factor receptor (EGFR) inhibition. Assays included a CAR activity reporter assay, EGF endocytosis assay, and EGFR phosphorylation assay. Docking simulations were used to identify putative binding sites for environmental chemicals on the EGFR. Whole-weight and lipid-adjusted serum mean pollutant exposures were determined using data from the National Health and Examination Survey (NHANES) and compared with the IC50 values determined in vitro. Chlordane, trans-nonachlor, PCB-126, PCB-153, and atrazine were the most potent EGFR inhibitors tested. PCB-126, PCB-153, and trans-nonachlor appeared to be competitive EGFR antagonists as they displaced bound EGF from EGFR. However, atrazine acted through a different mechanism and could be an EGFR tyrosine kinase inhibitor. EGFR inhibition relative effect potencies were determined for these compounds. In NHANES, serum concentrations of trans-nonachlor, PCB-126, and PCB-153 greatly exceeded their calculated IC50 values. A common mechanism of action through EGFR inhibition for three diverse classes of metabolic disrupting chemicals was characterized by measuring inhibition of EGFR phosphorylation and EGF-EGFR endocytosis. Based on NHANES data, EGFR inhibition may be an environmentally relevant mode of action for some PCBs, pesticides, and herbicides.

Indexed as

AnimalsCell Line, TumorConstitutive Androstane ReceptorEndocrine DisruptorsEndocytosisEpidermal Growth FactorErbB ReceptorsHep G2 CellsHumansMetabolic Networks and PathwaysMiceMolecular Docking SimulationPhosphorylationReceptors, Cytoplasmic and NuclearSignal TransductionTransfectionConstitutive Androstane ReceptorEndocrine DisruptorsEpidermal Growth FactorErbB ReceptorsReceptors, Cytoplasmic and Nuclear

Identifiers

PMID29329451
PMCPMC5888991
OpenAlexW2782620426

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.