Hydrogen Peroxide Enhances TGF{beta}-mediated Epithelial-to-Mesenchymal Transition in Human Mammary Epithelial MCF-10A Cells

Aim: 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. Materials and Methods: 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. Results: 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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