Transforming growth factor-beta (TGF-beta) is a cytokine Important in inducing epithelial-mesenchymal trinsition (EMT). a crucial morphological event in a wide range of physiological and pathological cellular processes. In this study, we demonstrate that TGF-beta 1 induces the EMT phenotype through decreasing the expression of the glutaredoxin 1 (Grx1) gene, an anti-oxidant enzyme, in H-Ras transformed EpH4 mammary epithelial cells (EpRas), but not in the parental EpH4 cells TGF-beta 1-induced reduction of Grx1 expression caused an increase of intracellular reactive oxygen species (ROS) in EpRas cells, and pre-treatment of the ROS scavenger N-acetylcysteine (NAC) inhibited TGF-beta 1-induced EMT Grx1-overexpressing EpRas cells showed a reduction in intracellular ROS generation and suppressed the expression of mesenchymal markers upon treatment of TGF-beta 1 In addition, MEK/MAP kinase and phosphatidylinositol-3 kinase (PI3K) signaling were found to mediate the decrease in Grx1 expression upon TGF-beta 1 treatment, depending on the presence of Ras protein Thus our findings strongly suggest that TGF-beta 1 promotes EMT by increasing intracellular ROS levels via down-regulation of the Grx1 gene in EpRas cells (C) 2009 Elsevier Inc All rights reserved