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Transcriptional and phenotypical alterations associated with a gradual benzo[a]pyrene-induced transition of human bronchial epithelial cells into mesenchymal-like cells
| Autoři | |
|---|---|
| Rok publikování | 2024 |
| Druh | Článek v odborném periodiku |
| Časopis / Zdroj | Environmental Toxicology and Pharmacology |
| Citace | |
| Doi | https://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 noncanonical Wnt pathway ligand WNT5A. This trend of up-regulation of pro-inflammatory genes and noncanonical Wnt pathway constituents was observed also in the BaP-transformed HBEC-12KT-B1 cells. In general, transcriptional effects of BaP differed from those of TGF beta 1, a prototypical EMT inducer, or a model nongenotoxic AhR ligand, TCDD. Carcinogenic polycyclic aromatic hydrocarbons could thus induce a unique set of molecular changes linked with EMT and cancer progression. |