TGF-beta targets the Wnt pathway components, APC and beta-catenin, as Mv1Lu cells undergo cell cycle arrest.
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.
Department of Pediatrics, University of Utah School of Medicine, Utah, USA.
Daniel J
DJ
Satterwhite
Kristi L
KL
Neufeld
D025601:Adenomatous Polyposis Coli Protein / Q000378:metabolism*; D000818:Animals; D002453:Cell Cycle / Q000502:physiology; D002460:Cell Line; D003598:Cytoskeletal Proteins / Q000378:metabolism* / Q000502:physiology; D004847:Epithelial Cells / Q000737:chemistry / Q000378:metabolism / Q000502:physiology; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D008168:Lung / Q000166:cytology; D008907:Mink; D012333:RNA, Messenger / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism* / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D051153:Wnt Proteins; D051176:beta Catenin
D025601:Adenomatous Polyposis Coli Protein; D003598:Cytoskeletal Proteins; D036341:Intercellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D015534:Trans-Activators; D016212:Transforming Growth Factor beta; D051153:Wnt Proteins; D051176:beta Catenin