Hydrogen peroxide negatively modulates Wnt signaling through downregulation of [beta]-catenin

The Wnt signal transduction pathway plays an important role in organogenesis and carcinogenesis. In an effort to better understand the action of oxidative stress-induced cellular signaling, we investigate the effect of exogenous H2O2on the Wnt signal pathway. H2O2decreases the amount of nuclear β-ca...

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Bibliographic Details
Published in:Cancer letters 2004-08, Vol.212 (2), p.225
Main Authors: Shin, Soon Young, Kim, Chang Gun, Jho, Eek-Hoon, Rho, Myung-Sun, Kim, Yong Sik, Kim, Young-Ho, Lee, Young Han
Format: Article
Language:English
Subjects:
Apoptosis
Binding sites
Deoxyribonucleic acid
DNA
Heparan sulfate
Kinases
Proteins
Rodents
Studies
Transcription factors
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Summary:The Wnt signal transduction pathway plays an important role in organogenesis and carcinogenesis. In an effort to better understand the action of oxidative stress-induced cellular signaling, we investigate the effect of exogenous H2O2on the Wnt signal pathway. H2O2decreases the amount of nuclear β-catenin and Tcf/Lef-dependent transcription. Overexpression of Dvl-1 abrogated H2O2-induced downregulation of β-catenin. Pretreatment with LiCl or Wnt-3a conditioned medium completely inhibited H2O2-induced release of mitochondrial cytochromecand DNA fragmentation. These results suggest that H2O2negatively modulates the Wnt signal pathway through downregulation of β-catenin.
ISSN:0304-3835
1872-7980
DOI:10.1016/j.canlet.2004.03.003