DOI: 10.1126/science.275.5307.1790 ISSN:

Stabilization of β-Catenin by Genetic Defects in Melanoma Cell Lines

Bonnee Rubinfeld, Paul Robbins, Mona El-Gamil, Iris Albert, Emilio Porfiri, Paul Polakis
  • Multidisciplinary

Signal transduction by β-catenin involves its posttranslational stabilization and downstream coupling to the Lef and Tcf transcription factors. Abnormally high amounts of β-catenin were detected in 7 of 26 human melanoma cell lines. Unusual messenger RNA splicing and missense mutations in the β-catenin gene (CTNNB1) that result in stabilization of the protein were identified in six of the lines, and the adenomatous polyposis coli tumor suppressor protein (APC) was altered or missing in two others. In the APC-deficient cells, ectopic expression of wild-type APC eliminated the excess β-catenin. Cells with stabilized β-catenin contained a constitutive β-catenin-Lef-1 complex. Thus, genetic defects that result in up-regulation of β-catenin may play a role in melanoma progression.

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