TGF-β Targets the Wnt Pathway Components, APC and β-catenin, as Mv1Lu Cells Undergo Cell Cycle Arrest

Abstract

The highly coordinated interaction of TGF-? and Wnt signaling pathways is critical for normal development. However, the effects of TGF-β on APC and beta-catenin, two key mediators of Wnt signaling in epithelial cells, have been largely unknown. We determined the effect of TGF-? on APC and beta-catenin expression in Mv1Lu, a non-transformed epithelial cell line, in which TGF-β signaling causes a G1 cell cycle arrest. We found that TGF-β rapidly reduced APC protein levels through a post-transcriptional mechanism. Further, TGF-beta increased beta-catenin mRNA and protein levels, and increased beta-catenin nuclear accumulation. Finally, retrovirus-mediated overexpression of beta-catenin discernibly enhanced the ability of TGF-β to induce a G1 cell cycle arrest. This is the first report demonstrating that TGF-β mimics the effect of Wnt signaling on beta-catenin in Mv1Lu cells, and that reduction of APC and nuclear accumulation of β-catenin have cooperative effects on mechanisms that mediate TGF-β-induced cell cycle arrest.