STABILIZATION OF BETA-CATENIN BY GENETIC-DEFECTS IN MELANOMA CELL-LINES

Signal transduction by beta-catenin involves its posttranslational sta bilization and downstream coupling to the Lef and Tcf transcription fa ctors, Abnormally high amounts of beta-catenin were detected in 7 of 2 6 human melanoma cell lines, Unusual messenger RNA splicing and missen se mutations in the beta-catenin gene (CTNNB1) that result in stabiliz ation of the protein were identified in six of the lines, and the aden omatous polyposis coli tumor suppressor protein (APC) was altered or m issing in two others, In the APC-deficient cells, ectopic expression o f wild-type APC eliminated the excess beta-catenin, Cells with stabili zed beta-catenin contained a constitutive beta-catenin-Lef-1 complex, Thus, genetic defects that result in up-regulation of beta-catenin may play a role in melanoma progression.