Daisuke Iizuka1, Megumi Sasatani1, Mary Helen Barcellos-Hoff2, Kenji Kamiya3. 1. Department of Experimental Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan. 2. Department of Radiation Oncology, University of California, San Francisco School of Medicine, San Francisco, CA, U.S.A. 3. Department of Experimental Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan kkamiya@hiroshima-u.ac.jp.
Abstract
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. Copyright
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. Copyright