P53 mutation as a source of aberrant beta-catenin accumulation in cancer cells

Oncogene. 2002 Nov 14;21(52):7971-80. doi: 10.1038/sj.onc.1205919.


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

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cytoskeletal Proteins / genetics
  • Cytoskeletal Proteins / metabolism*
  • Humans
  • Liver Neoplasms / genetics
  • Liver Neoplasms / metabolism*
  • Liver Neoplasms / pathology
  • Mutation*
  • Trans-Activators / genetics
  • Trans-Activators / metabolism*
  • Tumor Cells, Cultured
  • Tumor Suppressor Protein p53 / genetics*
  • beta Catenin


  • CTNNB1 protein, human
  • Cytoskeletal Proteins
  • Trans-Activators
  • Tumor Suppressor Protein p53
  • beta Catenin