Informace o publikaci

Transcriptional and phenotypical alterations associated with a gradual benzo[a]pyrene-induced transition of human bronchial epithelial cells into mesenchymal-like cells

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HÝŽĎALOVÁ Martina PROCHÁZKOVÁ Jiřina STRAKOVÁ Nicol PĚNČÍKOVÁ Kateřina STRAPÁČOVÁ Simona SLOVÁČKOVÁ Jana KAJABOVÁ Simona LÍBALOVÁ Helena TOPINKA Jan KABÁTKOVÁ Markéta VONDRÁČEK Jan MOLLERUP Steen MACHALA Miroslav

Rok publikování 2024
Druh Článek v odborném periodiku
Časopis / Zdroj Environmental Toxicology and Pharmacology
Fakulta / Pracoviště MU

Lékařská fakulta

Citace
www https://www.sciencedirect.com/science/article/pii/S1382668924000644
Doi http://dx.doi.org/10.1016/j.etap.2024.104424
Klíčová slova Benzo[a]pyrene; Aryl hydrocarbon receptor; 2 3 7 8-tetrachlorodibenzo-p-dioxin; Epithelial-mesenchymal transition; Human bronchial epithelial cells
Popis The role of benzo[a]pyrene (BaP), a prominent genotoxic carcinogen and aryl hydrocarbon receptor (AhR) ligand, in tumor progression remains poorly characterized. We investigated the impact of BaP on the process of epithelial-mesenchymal transition (EMT) in normal human bronchial epithelial HBEC-12KT cells. Early morphological changes after 2-week exposure were accompanied with induction of SERPINB2, IL1, CDKN1A/p21 (linked with cell cycle delay) and chemokine CXCL5. After 8-week exposure, induction of cell migration and EMT-related pattern of markers/regulators led to induction of further pro-inflammatory cytokines or non-canonical Wnt pathway ligand WNT5A. This trend of up-regulation of pro-inflammatory genes and non-canonical Wnt pathway constituents was observed also in the BaP-transformed HBEC-12KT-B1 cells. In general, transcriptional effects of BaP differed from those of TGFß1, a prototypical EMT inducer, or a model non-genotoxic AhR ligand, TCDD. Carcinogenic polycyclic aromatic hydrocarbons could thus induce a unique set of molecular changes linked with EMT and cancer progression.

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