Exogenous Expression of β-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).