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Hydrogen Peroxide Enhances TGFβ-mediated Epithelial-to-Mesenchymal Transition in Human Mammary Epithelial MCF-10A Cells.

  • Author(s): Iizuka, Daisuke
  • Sasatani, Megumi
  • Barcellos-Hoff, Mary Helen
  • Kamiya, Kenji
  • et al.
Abstract

This study investigated the effect of reactive oxygen species (ROS) on transforming growth factor (TGF)-β-mediated epithelial-to-mesenchymal transition (EMT) in order to clarify the influence of ROS and TGFβ on the induction of dysplasia and ultimately, tumorigenesis.Confluent MCF-10A human mammary epithelial cells were treated with H2O2 for 1 h, then reseeded at low density in the presence of TGFβ and cultured until confluence.Hydrogen peroxide (H2O2, 250 μM) enhanced TGFβ-mediated EMT, as evidenced by increased expression of EMT-associated transcription factors, which was accompanied by increased nuclear localization of phosphorylated SMAD family member 2 (SMAD2) and up-regulation of the TGFβ signaling pathway components mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK). Pharmacological inhibition of MEK/ERK signaling partly reversed the effects of H2O2 Conclusion: H2O2 enhances TGFβ-mediated EMT via SMAD and MEK/ERK signaling.

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