Decreased expression of glutaredoxin 1 is required for transforming growth factor-beta1-mediated epithelial-mesenchymal transition of EpRas mammary epithelial cells

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 d...

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Veröffentlicht in:Biochemical and biophysical research communications 2010-01, Vol.391 (1), p.1021-1027
Hauptverfasser: Lee, Eun Kyung, Jeon, Woo-Kwang, Chae, Min Young, Hong, Hye-Young, Lee, Youn Sook, Kim, Jun Hwan, Kwon, Jae Young, Kim, Byung-Chul, Park, Seok Hee
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Sprache:eng
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Zusammenfassung: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.
ISSN:1090-2104
DOI:10.1016/j.bbrc.2009.12.009