T cell factor-activated transcription is not sufficient to induce anchorage-independent growth of epithelial cells expressing mutant beta-catenin.
N-terminal mutations in beta-catenin that inhibit beta-catenin degradation are found in primary tumors and cancer cell lines, and increased beta-catenin/T cell factor (TCF)-activated transcription in these cells has been correlated with cancer formation. However, the role of mutant beta-catenin in cell transformation is poorly understood. Here, we compare the ability of different N-terminal mutations of beta-catenin (DeltaN131, DeltaN90, DeltaGSK) to induce TCF-activated transcription and anchorage-independent growth in Madin-Darby canine kidney epithelial cells. Expression of DeltaN90 or DeltaGSK beta-catenin increased TCF-activated transcription but did not induce significant anchorage-independent cell growth. In contrast, deletion of the alpha-catenin-binding site in DeltaN131 beta-catenin reduced TCF-activated transcription, compared with that induced by DeltaN90 or DeltaGSK beta-catenin, but significantly enhanced anchorage-independent cell growth.
Barth
A I
AI
Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA 94305-5345, USA. angelab@leland.stanford.edu
Stewart
D B
DB
Nelson
W J
WJ
D000818:Animals; D001483:Base Sequence; D002455:Cell Division / Q000235:genetics; D002471:Cell Transformation, Neoplastic; D003598:Cytoskeletal Proteins / Q000235:genetics*; D004285:Dogs; D004847:Epithelial Cells / Q000166:cytology*; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D015398:Signal Transduction / Q000235:genetics; D015534:Trans-Activators; D014157:Transcription Factors / Q000235:genetics*; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured; D051176:beta Catenin
C495270:CTNNB1 protein, human; D003598:Cytoskeletal Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D051176:beta Catenin