p53 mutation as a source of aberrant β-catenin accumulation in cancer cells

Date
2002
Authors
Cagatay, T.
Ozturk, M.
Advisor
Instructor
Source Title
Oncogene
Print ISSN
0950-9232
Electronic ISSN
Publisher
Volume
21
Issue
52
Pages
7971 - 7980
Language
English
Type
Article
Journal Title
Journal ISSN
Volume Title
Abstract

β-catenin is involved in both cell-cell interactions and wnt pathway-dependent cell fate determination through its interactions with E-cadherin and TCF/LEF transcription factors, respectively. Cytoplasmic/nuclear levels of β-catenin are important in regulated transcriptional activation of TCF/LEF target genes. Normally, these levels are kept low by proteosomal degradation of β-catenin through Axin1- and APC-dependent phosphorylation by CKI and GSK-3β. Deregulation of β-catenin degradation results in its aberrant accumulation, often leading to cancer. Accordingly, aberrant accumulation of β-catenin is observed at high frequency in many cancers. This accumulation correlates with either mutational activation of CTNNB1 (β-catenin) or mutational inactivation of APC and Axin1 genes in some tumors. However, there are many tumors that display β-catenin accumulation in the absence of a mutation in these genes. Thus, there must be additional sources for aberrant β-catenin accumulation in cancer cells. Here, we provide experimental evidence that wild-type β-catenin accumulates in hepatocellular carcinoma (HCC) cells in association with mutational inactivation of p53 gene. We also show that worldwide p53 and β-catenin mutation rates are inversely correlated in HCC. These data suggest that inactivation of p53 is an important cause of aberrant accumulation of β-catenin in cancer cells.

Course
Other identifiers
Book Title
Keywords
β-catenin, Hepatocellular carcinoma, Mutation, p53, wnt pathway, beta catenin, protein p53, article, carcinoma cell, clinical article, controlled study, correlation analysis, gene inactivation, gene mutation, human, human cell, liver cell carcinoma, priority journal, beta Catenin, Cytoskeletal Proteins, Humans, Liver Neoplasms, Mutation, Trans-Activators, Tumor Cells, Cultured, Tumor Suppressor Protein p53
Citation
Published Version (Please cite this version)