过氧化氢增强人乳腺上皮MCF-10A细胞中转化生长因子β介导的上皮-间质转化
Hydrogen Peroxide Enhances TGFβ-mediated Epithelial-to-Mesenchymal Transition in Human Mammary Epithelial MCF-10A Cells.
作者信息
Iizuka Daisuke, Sasatani Megumi, Barcellos-Hoff Mary Helen, Kamiya Kenji
机构信息
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.
出版信息
Anticancer Res. 2017 Mar;37(3):987-995. doi: 10.21873/anticanres.11408.
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.
目的
本研究调查了活性氧（ROS）对转化生长因子（TGF）-β介导的上皮-间质转化（EMT）的影响，以阐明ROS和TGFβ对发育异常诱导以及最终肿瘤发生的影响。
材料与方法
将汇合的MCF-10A人乳腺上皮细胞用H₂O₂处理1小时，然后在TGFβ存在下以低密度重新接种并培养至汇合。
结果
过氧化氢（H₂O₂，250μM）增强了TGFβ介导的EMT，EMT相关转录因子表达增加证明了这一点，同时伴有磷酸化SMAD家族成员2（SMAD2）核定位增加以及TGFβ信号通路成分丝裂原活化蛋白激酶激酶（MEK）/细胞外信号调节激酶（ERK）上调。MEK/ERK信号通路的药理学抑制部分逆转了H₂O₂的作用。结论：H₂O₂通过SMAD和MEK/ERK信号通路增强TGFβ介导的EMT。
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