Adaptive changes in global gene expression profile of lung carcinoma A549 cells acutely exposed to distinct types of AhR ligands

PROCHÁZKOVÁ, Jiřina, Simona STRAPÁČOVÁ, Lucie SVRŽKOVÁ, Zdeněk ANDRYSÍK, Martina HYZDALOVA, Eva HRUBÁ, Kateřina PĚNČÍKOVÁ, H LIBALOVA, J TOPINKA, Jiří KLÉMA, JM ESPINOSA, Jan VONDRÁČEK and Miroslav MACHALA. Adaptive changes in global gene expression profile of lung carcinoma A549 cells acutely exposed to distinct types of AhR ligands. Toxicology Letters. CLARE: Elsevier, 2018, vol. 292, p. 162-174. ISSN 0378-4274. Available from: https://dx.doi.org/10.1016/j.toxlet.2018.04.024.

Basic information

• Original name: Adaptive changes in global gene expression profile of lung carcinoma A549 cells acutely exposed to distinct types of AhR ligands
• Authors: PROCHÁZKOVÁ, Jiřina, Simona STRAPÁČOVÁ, Lucie SVRŽKOVÁ, Zdeněk ANDRYSÍK, Martina HYZDALOVA, Eva HRUBÁ, Kateřina PĚNČÍKOVÁ, H LIBALOVA, J TOPINKA, Jiří KLÉMA, JM ESPINOSA, Jan VONDRÁČEK and Miroslav MACHALA.
• Edition: Toxicology Letters, CLARE, Elsevier, 2018, 0378-4274.

Other information

• Original language: English
• Type of outcome: Article in a journal
• Confidentiality degree: is not subject to a state or trade secret
• WWW: URL
• Impact factor: Impact factor: 3.499
• Doi: http://dx.doi.org/10.1016/j.toxlet.2018.04.024
• UT WoS: 000433259100018
• Keywords in English: Aryl hydrocarbon receptor; Lung cancer; Dioxins; Global gene expression profiling
• Tags: RIV ne

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/beta-cat, IFN., 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.