Attenuation of the Wnt/b-catenin/TCF pathway by in vivo interferon-a2b (IFN-a2b) treatment in preneoplastic rat livers

Wnt/b-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 b-catenin binding, particularly under cellular oxidative stress conditions. Contrary to b-catenin/TCF, b-catenin/FOXO promotes the transcription of genes involved in cell cycle arrest and apoptosis. We have previously demonstrated that in vivo interferon-a2b (IFN-a2b) administration induces apoptosis in preneoplastic livers, a mechanism mediated by reactive oxygen species (ROS) and transforming growth factor-b1 (TGF-b1). This study was aimed to assess the status of the Wnt/b-catenin/TCF pathway in a very early stage of rat hepatocarcinogenesis and to further evaluate the effects of in vivo IFN-a2b treatment on it. We demonstrated that the Wnt/b-catenin/TCF pathway is activated in preneoplastic rat livers. More important, in vivo IFN-a2b treatment inhibits Wnt/b-catenin/TCF pathway and promotes programed cell death possibly providing a link with FOXO pathway.