Stabilization of β-Catenin by Genetic Defects in Melanoma Cell Lines
摘要:
Signal transduction by β-catenin involves its posttranslational stabilization and down-stream 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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关键词:
Cell Line Tumor Cells, Cultured Animals Humans Mice Melanoma Cytoskeletal Proteins Adenomatous Polyposis Coli Protein DNA-Binding Proteins Trans-Activators
DOI:
10.1126/science.275.5307.1790
被引量:
年份:
1997






































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