title: Atrazine represses S100A4 gene expression and TPA-induced motility in HepG2 cells.
abstract: Atrazine (ATZ) is probably the most widely used herbicide in the world. However there are still many controversies regarding its impacts on human health. Our investigations on the role of pesticides in liver dysfunctions have led us to detect an inhibition of FSP1 expression of 70% at 50μm and around 95% at 500μM of ATZ (p<0.01). This gene encodes the protein S100a4 and is a clinical biomarker of epithelial-mesenchymal transition (EMT), a key step in the metastatic process. Here we investigated the possible effect of ATZ on cell migration and noticed that it prevents the EMT and motility of the HepG2 cells induced by the phorbol ester TPA. ATZ decreases Fak pathway activation but has no effect on the Erk1/2 pathway known to be involved in metastasis in this cell line. These results suggest that ATZ could be involved in cell homeostasis perturbation, potentially through a S100a4-dependant mechanism.
authors.affiliation: Laboratoire de Toxicologie Cellulaire, Moléculaire des Xénobiotiques, INRA, UMR 1331 TOXALIM Sophia Antipolis, 06903 Sophia Antipolis, France. Electronic address: ludovic.peyre@sophia.inra.fr.
authors.forename: Ludovic
authors.initials: L
authors.lastname: Peyre
authors.affiliation: Laboratoire de Toxicologie Cellulaire, Moléculaire des Xénobiotiques, INRA, UMR 1331 TOXALIM Sophia Antipolis, 06903 Sophia Antipolis, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Zucchini-Pascal
authors.affiliation: Laboratoire de Toxicologie Cellulaire, Moléculaire des Xénobiotiques, INRA, UMR 1331 TOXALIM Sophia Antipolis, 06903 Sophia Antipolis, France.
authors.forename: Roger
authors.initials: R
authors.lastname: Rahmani
mesh_terms: D001280:Atrazine / Q000633:toxicity*; D015153:Blotting, Western; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects*; D005353:Fibronectins / Q000096:biosynthesis; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects; D006540:Herbicides / Q000633:toxicity*; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects; D060888:Real-Time Polymerase Chain Reaction; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins / Q000096:biosynthesis*; D015398:Signal Transduction / Q000187:drug effects; D013755:Tetradecanoylphorbol Acetate / Q000037:antagonists & inhibitors* / Q000494:pharmacology*
chemical_list: C067625:FN1 protein, human; D005353:Fibronectins; D006540:Herbicides; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins; C077591:S100A4 protein, human; D051416:Focal Adhesion Protein-Tyrosine Kinases; D013755:Tetradecanoylphorbol Acetate; D001280:Atrazine
keywords: Atrazine; Cell migration; Epithelial-to-mesenchymal transition; HepG2; S100A4