Hydrogen Peroxide Enhances TGFβ-mediated Epithelial-to-Mesenchymal Transition in Human Mammary Epithelial MCF-10A Cells.
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 H2O2for 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 H2O2Conclusion: H2O2enhances TGFβ-mediated EMT via SMAD and MEK/ERK signaling.
Department of Experimental Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan.
Daisuke
D
Iizuka
Department of Experimental Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan.
Megumi
M
Sasatani
Department of Radiation Oncology, University of California, San Francisco School of Medicine, San Francisco, CA, U.S.A.
Mary Helen
MH
Barcellos-Hoff
Department of Experimental Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan kkamiya@hiroshima-u.ac.jp.
Kenji
K
Kamiya
D015703:Antigens, CD / Q000378:metabolism; D001943:Breast Neoplasms / Q000378:metabolism*; D015820:Cadherins / Q000378:metabolism; D045744:Cell Line, Tumor; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D006861:Hydrogen Peroxide / Q000737:chemistry*; D008856:Microscopy, Fluorescence; D018384:Oxidative Stress; D010766:Phosphorylation; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction; D051899:Smad2 Protein / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D015703:Antigens, CD; C513384:CDH1 protein, human; C050361:CDH2 protein, human; D015820:Cadherins; D017382:Reactive Oxygen Species; C497782:SMAD2 protein, human; D051899:Smad2 Protein; D016212:Transforming Growth Factor beta; D006861:Hydrogen Peroxide; D048049:Extracellular Signal-Regulated MAP Kinases
EMT; Epithelial-to-mesenchymal transition; H2O2; TGFβ