Atrazine represses S100A4 gene expression and TPA-induced motility in HepG2 cells

Ludovic Peyre; Nathalie Zucchini-Pascal; Roger Rahmani

doi:10.1016/j.tiv.2013.10.019

Atrazine represses S100A4 gene expression and TPA-induced motility in HepG2 cells

Toxicol In Vitro. 2014 Mar;28(2):156-63. doi: 10.1016/j.tiv.2013.10.019. Epub 2013 Nov 6.

Authors

Ludovic Peyre¹, Nathalie Zucchini-Pascal², Roger Rahmani²

Affiliations

¹ Laboratoire de Toxicologie Cellulaire, Moléculaire des Xénobiotiques, INRA, UMR 1331 TOXALIM Sophia Antipolis, 06903 Sophia Antipolis, France. Electronic address: ludovic.peyre@sophia.inra.fr.
² Laboratoire de Toxicologie Cellulaire, Moléculaire des Xénobiotiques, INRA, UMR 1331 TOXALIM Sophia Antipolis, 06903 Sophia Antipolis, France.

PMID: 24211529
DOI: 10.1016/j.tiv.2013.10.019

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.

Keywords: Atrazine; Cell migration; Epithelial-to-mesenchymal transition; HepG2; S100A4.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Atrazine / toxicity*
Blotting, Western
Cell Line
Cell Movement / drug effects*
Fibronectins / biosynthesis
Focal Adhesion Protein-Tyrosine Kinases / drug effects
Gene Expression / drug effects
Herbicides / toxicity*
Humans
MAP Kinase Signaling System / drug effects
Real-Time Polymerase Chain Reaction
S100 Calcium-Binding Protein A4
S100 Proteins / biosynthesis*
Signal Transduction / drug effects
Tetradecanoylphorbol Acetate / antagonists & inhibitors*
Tetradecanoylphorbol Acetate / pharmacology*

Substances

FN1 protein, human
Fibronectins
Herbicides
S100 Calcium-Binding Protein A4
S100 Proteins
S100A4 protein, human
Focal Adhesion Protein-Tyrosine Kinases
Tetradecanoylphorbol Acetate
Atrazine