AI Article Synopsis
- TGF-beta1 promotes epithelial-mesenchymal transition (EMT) by decreasing the expression of the antioxidant enzyme glutaredoxin 1 (Grx1) in H-Ras transformed mammary epithelial cells.
- The reduction of Grx1 leads to increased levels of reactive oxygen species (ROS), which are linked to the EMT process.
- Inhibition of ROS with a scavenger and overexpression of Grx1 can suppress TGF-beta1-induced EMT, indicating that ERK/MAPK and PI3K signaling pathways play a role in this process.
Article Abstract
Transforming growth factor-beta (TGF-beta) is a cytokine important in inducing epithelial-mesenchymal transition (EMT), a crucial morphological event in a wide range of physiological and pathological cellular processes. In this study, we demonstrate that TGF-beta1 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-beta1-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-beta1-induced EMT. Grx1-overexpressing EpRas cells showed a reduction in intracellular ROS generation and suppressed the expression of mesenchymal markers upon treatment of TGF-beta1. In addition, MEK/MAP kinase and phosphatidylinositol-3 kinase (PI3K) signaling were found to mediate the decrease in Grx1 expression upon TGF-beta1 treatment, depending on the presence of Ras protein. Thus our findings strongly suggest that TGF-beta1 promotes EMT by increasing intracellular ROS levels via down-regulation of the Grx1 gene in EpRas cells.
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| http://dx.doi.org/10.1016/j.bbrc.2009.12.009 | DOI Listing |
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