| Popis: |
The highly coordinated interaction of TGF-beta and Wnt signaling pathways is critical for normal development. However, the effects of TGF-beta on APC and beta-catenin, two key mediators of Wnt signaling in epithelial cells, have been largely unknown. We determined the effect of TGF-beta on APC and beta-catenin expression in Mv1Lu, a nontransformed epithelial cell line, in which TGF-beta signaling causes a G(1) cell cycle arrest. We found that TGF-beta 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-beta to induce a G(1) cell cycle arrest. This is the first report demonstrating that TGF-beta mimics the effect of Wnt signaling on beta-catenin in Mv1Lu cells, and that reduction of APC and nuclear accumulation of beta-catenin have cooperative effects on mechanisms that mediate TGF-beta-induced cell cycle arrest. |
