Science  1997 Mar 21;275(5307):1790-2 

Comment in:
 Science. 1997 Mar 21;275(5307):1752-3.

Stabilization of beta-catenin by genetic defects in melanoma cell lines.

Rubinfeld B, Robbins P, El-Gamil M, Albert I, Porfiri E, Polakis P.

Onyx Pharmaceuticals, 3031 Research Drive, Richmond, CA 94806, USA.

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.

PMID: 9065403 [PubMed - indexed for MEDLINE]