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

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-cat...

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Bibliographic Details
Published in:Science (American Association for the Advancement of Science) 1997-03, Vol.275 (5307), p.1790-1792
Main Authors: Rubinfeld, Bonnee, Robbins, Paul, El-Gamil, Mona, Albert, Iris, Porfiri, Emilio, Polakis, Paul
Format: Article
Language:English
Subjects:
Adenomatous Polyposis Coli Protein
Animals
Antibodies
beta Catenin
Biological and medical sciences
Cancer
Cell Line
Cell lines
Cell physiology
Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes
Colorectal cancer
Complementary DNA
Cytoskeletal Proteins - chemistry
Cytoskeletal Proteins - genetics
Cytoskeletal Proteins - metabolism
DNA-Binding Proteins - metabolism
Exons
Fundamental and applied biological sciences. Psychology
Gene Expression Regulation, Neoplastic
Genes, APC
Genetic aspects
Genetic Disorders
Genetic mutation
Genetics
Humans
Immunoblotting
Lymphoid Enhancer-Binding Factor 1
Medical research
Melanoma
Melanoma - genetics
Melanoma - metabolism
Messenger RNA
Mice
Molecular and cellular biology
Mutation
Point Mutation
Proteins
RNA Splicing
RNA, Messenger - genetics
RNA, Neoplasm - genetics
Skin cancer
Trans-Activators
Transcription Factors - metabolism
Transfection
Tumor cell line
Tumor Cells, Cultured
Up-Regulation
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Summary: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.
ISSN:0036-8075
1095-9203
DOI:10.1126/science.275.5307.1790