Informace o publikaci

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

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PROCHÁZKOVÁ Jiřina STRAPÁČOVÁ Simona SVRŽKOVÁ Lucie ANDRYSÍK Zdeněk HYZDALOVA Martina HRUBÁ Eva PĚNČÍKOVÁ Kateřina LIBALOVA H TOPINKA J KLÉMA Jiří ESPINOSA JM VONDRÁČEK Jan MACHALA Miroslav

Rok publikování 2018
Druh Článek v odborném periodiku
Časopis / Zdroj Toxicology Letters
Citace
www http://dx.doi.org/10.1016/j.toxlet.2018.04.024
Doi http://dx.doi.org/10.1016/j.toxlet.2018.04.024
Klíčová slova Aryl hydrocarbon receptor; Lung cancer; Dioxins; Global gene expression profiling
Popis 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.

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