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

作者：Iizuka Daisuke; Sasatani Megumi; Barcellos Hoff Mary Helen; Kamiya Kenji^*

来源：Anticancer Research, 2017, 37(3): 987-995.

DOI：10.21873/anticanres.11408

• Epithelial-to-mesenchymal transition
• H2O2
• TGF beta
• EMT

Aim: This study investigated the effect of reactive oxygen species (ROS) on transforming growth factor (TGF)- beta - mediated epithelial-to-mesenchymal transition (EMT) in order to clarify the influence of ROS and TGF beta 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 beta and cultured until confluence. Results: Hydrogen peroxide (H2O2, 250 mu M) enhanced TGFamediated 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 TGF beta 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 beta-mediated EMT via SMAD and MEK/ERK signaling.

• 出版日期2017-3