FUNCTIONAL EVALUATION OF 0 -CATENIN GENE MUTATIONS IN TUMOR DEVELOPMENT : EFFECTS OF β-CATENIN MUTANTS ON CELL MOTILITY AND GENE EXPRESSION

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β-catenin plays a crucial role in the formation and maintenance of cell-cell adhesions in epithelial tissues. It is also an important member of Wnt signaling pathway that is involved in several aspects of development and morphogenesis. Wnt signal results in the accumulation of cytosolic and nuclear levels of β-catenin, which is normally maitained at a low level through the degradation process via proteasome. Intracellualr accumulation of β-catenin is also found in a number of human cancers where a variety of mutations in β-catenin gene have been reported. We previously developed a mutation database (Mutation View) for human disease genes. In this study, we have collected 441 cases for the mutation of β-catenin gene and entered these data into Mutation View. This entry clearly shows us that a variety of mutation types such as deletion and missense occur maily in exon 3 of β-catenin gene. Especially, the missense mutations affect serines in exon 3 that have been implicated in the down-regulation of B -catenin through phosphorylation by the GSK-3 kinase. To understand the molecular mechanism by which up-regulation of β-catenin plays a role in tumor formation, we transfected four types of cell lines with wild type or mutant types (S33C and S45F) of β-catenin. At present, we screen cell lines with elevated amounts of these wild and mutant proteins.