Adaptive changes in global gene expression profile of lung carcinoma A549 cells acutely exposed to distinct types of AhR ligands
Language English Country Netherlands Media print-electronic
Document type Journal Article
PubMed
29704546
DOI
10.1016/j.toxlet.2018.04.024
PII: S0378-4274(18)30158-9
Knihovny.cz E-resources
- Keywords
- Aryl hydrocarbon receptor, Dioxins, Global gene expression profiling, Lung cancer,
- MeSH
- Transcriptional Activation drug effects MeSH
- Azo Compounds toxicity MeSH
- Benzo(a)pyrene toxicity MeSH
- A549 Cells MeSH
- Time Factors MeSH
- Fluorenes toxicity MeSH
- Transcription, Genetic drug effects MeSH
- Gene Regulatory Networks drug effects MeSH
- Indoles toxicity MeSH
- Carbazoles toxicity MeSH
- Environmental Pollutants toxicity MeSH
- Humans MeSH
- Ligands MeSH
- Lung Neoplasms genetics metabolism MeSH
- Polychlorinated Dibenzodioxins toxicity MeSH
- Pyrazoles toxicity MeSH
- Receptors, Aryl Hydrocarbon agonists metabolism MeSH
- Gene Expression Regulation, Neoplastic drug effects MeSH
- Oligonucleotide Array Sequence Analysis MeSH
- Signal Transduction drug effects MeSH
- Gene Expression Profiling methods MeSH
- Thiazoles toxicity MeSH
- Basic Helix-Loop-Helix Transcription Factors agonists metabolism MeSH
- Transcriptome drug effects MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- 2-(1'H-indole-3'-carbonyl)thiazole-4-carboxylic acid methyl ester MeSH Browser
- 2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazophenyl)amide MeSH Browser
- 6-formylindolo(3,2-b)carbazole MeSH Browser
- AHR protein, human MeSH Browser
- Azo Compounds MeSH
- benzo(k)fluoranthene MeSH Browser
- Benzo(a)pyrene MeSH
- Fluorenes MeSH
- Indoles MeSH
- Carbazoles MeSH
- Environmental Pollutants MeSH
- Ligands MeSH
- Polychlorinated Dibenzodioxins MeSH
- Pyrazoles MeSH
- Receptors, Aryl Hydrocarbon MeSH
- Thiazoles MeSH
- Basic Helix-Loop-Helix Transcription Factors MeSH
Exposure to persistent ligands of aryl hydrocarbon receptor (AhR) has been found to cause lung cancer in experimental animals, and lung adenocarcinomas are often associated with enhanced AhR expression and aberrant AhR activation. In order to better understand the action of toxic AhR ligands in lung epithelial cells, we performed global gene expression profiling and analyze TCDD-induced changes in A549 transcriptome, both sensitive and non-sensitive to CH223191 co-treatment. Comparison of our data with results from previously reported microarray and ChIP-seq experiments enabled us to identify candidate genes, which expression status reflects exposure of lung cancer cells to TCDD, and to predict processes, pathways (e.g. ER stress, Wnt/β-cat, IFNɣ, EGFR/Erbb1), putative TFs (e.g. STAT, AP1, E2F1, TCF4), which may be implicated in adaptive response of lung cells to TCDD-induced AhR activation. Importantly, TCDD-like expression fingerprint of selected genes was observed also in A549 cells exposed acutely to both toxic (benzo[a]pyrene, benzo[k]fluoranthene) and endogenous AhR ligands (2-(1H-Indol-3-ylcarbonyl)-4-thiazolecarboxylic acid methyl ester and 6-formylindolo[3,2-b]carbazole). Overall, our results suggest novel cellular candidates, which could help to improve monitoring of AhR-dependent transcriptional activity during acute exposure of lung cells to distinct types of environmental pollutants.
Department of Chemistry and Toxicology Veterinary Research Institute Brno Czech Republic
Department of Computer Science Czech Technical University Prague Czech Republic
References provided by Crossref.org
