Adaptive changes in global gene expression profile of lung carcinoma A549 cells acutely exposed to distinct types of AhR ligands. (August 2018)

• Record Type: Journal Article
• Authors: Procházková, Jiřina; Strapáčová, Simona; Svržková, Lucie; Andrysík, Zdeněk; Hýžďalová, Martina; Hrubá, Eva; Pěnčíková, Kateřina; Líbalová, Helena; Topinka, Jan; Kléma, Jiří; Espinosa, Joaquín M.; Vondráček, Jan; Machala, Miroslav
• Is Part Of: Toxicology letters. Volume 292(2018)
• Page Start: 162
• Page End: 174
• Publication Date: 2018-08
• Subjects: Aryl hydrocarbon receptor -- Lung cancer -- Dioxins -- Global gene expression profiling; Toxicology -- Periodicals; 363.179
• DOI: 10.1016/j.toxlet.2018.04.024
• Languages: English
• ISSNs: 0378-4274

Abstract

Graphical abstract: Highlights: Global gene profiling of AhR-dependent changes in lung cancer cells transcriptome. Acute exposure to TCDD, BaP, BkF, ITE and FICZ shows common expression fingerprint. Suggestion of specific novel cellular candidates for monitoring of TCDD exposure. GREM1, HIPK2, SOX9, ID1 proposed as novel gene sensors of AhR activity in lung cells. Prediction of activation status of pathways/processes during acute TCDD exposure. Abstract: 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-(1 H -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.