Attenuation of the Wnt/beta-catenin/TCF pathway by in vivo interferon-alpha2b (IFN-alpha2b) treatment in preneoplastic rat livers.
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.
Parody
Juan P
JP
Instituto de Fisiología Experimental, Consejo Nacional de Investigaciones Científicas y T écnicas (CONICET), 2000 Rosario, Argentina.
Alvarez
Maria L
ML
Quiroga
Ariel D
AD
Ceballos
Maria P
MP
Frances
Daniel E
DE
Pisani
Gerardo B
GB
Pellegrino
Jose M
JM
Carnovale
Cristina E
CE
Carrillo
Maria C
MC
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000494:pharmacology*; D008114:Liver Neoplasms, Experimental / Q000378:metabolism*; D008297:Male; D011230:Precancerous Conditions / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins; D051820:TCF Transcription Factors / Q000378:metabolism*; D051153:Wnt Proteins / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism*
D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D051820:TCF Transcription Factors; D051153:Wnt Proteins; D051176:beta Catenin