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
Instituto de Fisiología Experimental, Consejo Nacional de Investigaciones Científicas y T écnicas (CONICET), 2000 Rosario, Argentina.
Growth Factors. 2010 Jun;28(3):166-77. doi: 10.3109/08977190903547863.
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.
Wnt/β-连环蛋白/T细胞因子（TCF）信号通路在多种人类癌症中被激活，可促进细胞生长和增殖。含叉头框O类（FOXO）转录因子与TCF竞争结合β-连环蛋白，尤其在细胞氧化应激条件下。与β-连环蛋白/TCF相反，β-连环蛋白/FOXO可促进参与细胞周期停滞和凋亡相关基因的转录。我们之前已证明，体内给予干扰素α2b（IFN-α2b）可诱导癌前肝脏发生凋亡，这一机制由活性氧（ROS）和转化生长因子β1（TGF-β1）介导。本研究旨在评估大鼠肝癌发生极早期阶段Wnt/β-连环蛋白/TCF信号通路的状态，并进一步评估体内IFN-α2b治疗对该通路的影响。我们证明Wnt/β-连环蛋白/TCF信号通路在癌前大鼠肝脏中被激活。更重要的是，体内IFN-α2b治疗可抑制Wnt/β-连环蛋白/TCF信号通路并促进程序性细胞死亡，这可能与FOXO信号通路存在联系。
