Stabilization of beta-catenin by genetic defects in melanoma cell lines.
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.
Rubinfeld
B
B
Onyx Pharmaceuticals, 3031 Research Drive, Richmond, CA 94806, USA.
Robbins
P
P
El-Gamil
M
M
Albert
I
I
Porfiri
E
E
Polakis
P
P
D025601:Adenomatous Polyposis Coli Protein; D000818:Animals; D002460:Cell Line; D003598:Cytoskeletal Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D017491:Genes, APC; D006801:Humans; D051821:Lymphoid Enhancer-Binding Factor 1; D008545:Melanoma / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D009154:Mutation; D017354:Point Mutation; D012326:RNA Splicing; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D015534:Trans-Activators; D014157:Transcription Factors / Q000378:metabolism; D014162:Transfection; D014407:Tumor Cells, Cultured; D015854:Up-Regulation; D051176:beta Catenin
D025601:Adenomatous Polyposis Coli Protein; C495270:CTNNB1 protein, human; C495267:CTNNB1 protein, mouse; D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins; D051821:Lymphoid Enhancer-Binding Factor 1; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D015534:Trans-Activators; D014157:Transcription Factors; D051176:beta Catenin