Attenuation of the Wnt/β-catenin/TCF pathway by in vivo interferon-α2b (IFN-α2b) treatment in preneoplastic rat livers

Abstract

Wnt/β-catenin/T cell factor (TCF) pathway is activated in several types of human cancers, promoting cell growth and proliferation. Forkhead box containing protein class O (FOXO) transcription factors compete with TCF for β-catenin binding, particularly under cellular oxidative stress conditions. Contrary to β-catenin/TCF, β-catenin/FOXO promotes the transcription of genes involved in cell cycle arrest and apoptosis. We have previously demonstrated that in vivo interferon-α2b (IFN-α2b) administration induces apoptosis in preneoplastic livers, a mechanism mediated by reactive oxygen species (ROS) and transforming growth factor-β₁ (TGF-β₁). This study was aimed to assess the status of the Wnt/β-catenin/TCF pathway in a very early stage of rat hepatocarcinogenesis and to further evaluate the effects of in vivo IFN-α2b treatment on it. We demonstrated that the Wnt/β-catenin/TCF pathway is activated in preneoplastic rat livers. More important, in vivo IFN-α2b treatment inhibits Wnt/β-catenin/TCF pathway and promotes programed cell death possibly providing a link with FOXO pathway.

Keywords::

• Hepatocarcinogenesis
• β-catenin
• TCF
• FOXO
• oxidative stress

Declaration of interest: This work was supported by Research Grant PICT 05-38068 (MC Carrillo) from Agencia Nacional de Promocio'n Cient'fica y Tecnolo'gica (ANPCyT). The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.