Attenuation of the Wnt/beta-catenin/TCF pathway by in vivo interferon-alpha 2b (IFN-alpha 2b) treatment in preneoplastic rat livers

作者：Parody Juan P; Alvarez Maria L; Quiroga Ariel D; Ceballos Maria P; Frances Daniel E; Pisani Gerardo B; Pellegrino Jose M; Carnovale Cristina E; Carrillo Maria C^*

来源：Growth Factors, 2010, 28(3): 166-177.

DOI：10.3109/08977190903547863

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

Wnt/beta-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 beta-catenin binding, particularly under cellular oxidative stress conditions. Contrary to beta-catenin/TCF, beta-catenin/FOXO promotes the transcription of genes involved in cell cycle arrest and apoptosis. We have previously demonstrated that in vivo interferon-alpha 2b (IFN-alpha 2b) administration induces apoptosis in preneoplastic livers, a mechanism mediated by reactive oxygen species (ROS) and transforming growth factor-beta(1) (TGF-beta(1)). This study was aimed to assess the status of the Wnt/beta-catenin/TCF pathway in a very early stage of rat hepatocarcinogenesis and to further evaluate the effects of in vivo IFN-alpha 2b treatment on it. We demonstrated that the Wnt/beta-catenin/TCF pathway is activated in preneoplastic rat livers. More important, in vivo IFN-alpha 2b treatment inhibits Wnt/beta-catenin/TCF pathway and promotes programed cell death possibly providing a link with FOXO pathway.

• 出版日期2010-6