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

JUAN P. PARODY; MARIA L. ALVAREZ; ARIEL D. QUIROGA; MARIA P. CEBALLOS; DANIEL E. FRANCES; GERARDO B. PISANI; JOSE M. PELLEGRINO; CRISTINA E. CARNOVALE; MARIA C. CARRILLO

GROWTH FACTORS

TAYLOR & FRANCIS LTD

Año: 2010 p. 166 - 177

0897-7194

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-alpha2b (IFN-alpha2b) 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-alpha2b treatment on it. We demonstrated that the Wnt/beta-catenin/TCF pathway is activated in preneoplastic rat livers. More important, in vivo IFN-alpha2b treatment inhibits Wnt/beta-catenin/TCF pathway and promotes programed cell death possibly providing a link with FOXO pathway.