Hydrogen peroxide enhances tgf-mediated epithelial-to-mesenchymal transition in human mammary epithelial mcf-10a cells

Abstract

Aim: This study investigated the effect of reactive oxygen species (ROS) on transforming growth factor (TGF)-mediated epithelial-to-mesenchymal transition (EMT) in order to clarify the influence of ROS and TGF 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 TGF and cultured until confluence. Results: Hydrogen peroxide (H2O2, 250 M) enhanced TGF-mediated EMT, as evidenced by increased expression of EMTassociated transcription factors, which was accompanied by increased nuclear localization of phosphorylated SMAD family member 2 (SMAD2) and up-regulation of the TGF 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 TGF-mediated EMT via SMAD and MEK/ERK signaling.