Stabilization of beta-catenin by genetic defects in melanoma cell lines
Rubinfeld, B.; Robbins, P.; El-Gamil, M.; Albert, I.; Porfiri, E.; Polakis, P.
Science 275(5307): 1790-1792
1997
ISSN/ISBN: 0036-8075 PMID: 9065403 Document Number: 481668
Signal transduction by beta-catenin involves its posttranslational stabilization and down-stream coupling to the Lef and Tcf transcription factors. Abnormally high amounts of beta-catenin were detected in 7 of 26 human melanoma cell lines. Unusual messenger RNA splicing and missense mutations in the beta-catenin gene (CTNNB1) that result in stabilization of the protein were identified in six of the lines, and the adenomatous polyposis coil tumor suppressor protein (APC) was altered or missing in two others. In the APCdeficient cells, ectopic expression of wild-type APC eliminated the excess beta-catenin. Cells with stabilized 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.