Exogenous expression of beta-catenin regulates contact inhibition, anchorage-independent growth, anoikis, and radiation-induced cell cycle arrest.
beta-Catenin is an important regulator of cell-cell adhesion and embryonic development that associates with and regulates the function of the LEF/TCF family of transcription factors. Mutations of beta-catenin and the tumor suppressor gene, adenomatous polyposis coli, occur in human cancers, but it is not known if, and by what mechanism, increased beta-catenin causes cellular transformation. This study demonstrates that modest overexpression of beta-catenin in a normal epithelial cell results in cellular transformation. These cells form colonies in soft agar, survive in suspension, and continue to proliferate at high cell density and following gamma-irradiation. Endogenous cytoplasmic beta-catenin levels and signaling activity were also found to oscillate during the cell cycle. Taken together, these data demonstrate that beta-catenin functions as an oncogene by promoting the G(1) to S phase transition and protecting cells from suspension-induced apoptosis (anoikis).
Orford
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The Lombardi Cancer Center and the Department of Cell Biology, Georgetown University School of Medicine, Washington, District of Columbia 20007, USA.
Orford
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Byers
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D000818:Animals; D017209:Apoptosis; D002452:Cell Count / Q000528:radiation effects; D002453:Cell Cycle / Q000528:radiation effects*; D002460:Cell Line; D048429:Cell Size; D002471:Cell Transformation, Neoplastic / Q000528:radiation effects; D003260:Contact Inhibition / Q000528:radiation effects; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000502:physiology*; D004285:Dogs; D005720:Gamma Rays; D015870:Gene Expression; D007399:Interphase / Q000528:radiation effects; D008954:Models, Biological; D009154:Mutation; D009857:Oncogenes / Q000235:genetics / Q000502:physiology; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D015534:Trans-Activators; D019076:Transgenes / Q000235:genetics; D051176:beta Catenin
D003598:Cytoskeletal Proteins; D011993:Recombinant Fusion Proteins; D015534:Trans-Activators; D051176:beta Catenin