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Science 21 March 1997:
Vol. 275. no. 5307, pp. 1790 - 1792
DOI: 10.1126/science.275.5307.1790
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Reports

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

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

Signal transduction by beta -catenin involves its posttranslational stabilization and downstream 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 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 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.

B. Rubinfeld, I. Albert, E. Porfiri, P. Polakis, Onyx Pharmaceuticals, 3031 Research Drive, Richmond, CA 94806, USA.
P. Robbins and M. El-Gamil, Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
*   To whom correspondence should be addressed. E-mail: paul{at}onyx-pharm.com

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Science. ISSN 0036-8075 (print), 1095-9203 (online)