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

Daisuke Iizuka, Megumi Sasatani, Mary Helen Barcellos-Hoff, Kenji Kamiya

Journal: Anticancer research 2017;37(3):987-995

PMID: 28314256

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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 HO for 1 h, then reseeded at low density in the presence of TGFβ and cultured until confluence.

RESULTS

Hydrogen peroxide (HO, 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 HO Conclusion: HO enhances TGFβ-mediated EMT via SMAD and MEK/ERK signaling.

Address: Department of Experimental Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan.; Department of Radiation Oncology, University of California, San Francisco School of Medicine, San Francisco, CA, U.S.A.; Department of Experimental Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan [email protected].

DOI: 10.21873/anticanres.11408