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

Oncogene volume 21, pages 7971–7980 (2002)Cite this article

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.

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Acknowledgements

This work was supported by grants from Tubitak and Bilkent University. We thank S Friend (USA) and T Frebourg (France) for p53 expression plasmids and T Arayici for technical help in DNA sequencing.

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  1. Department of Molecular Biology and Genetics, Bilkent University, Ankara, 06533, Turkey

    Tolga Cagatay & Mehmet Ozturk

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  1. Tolga Cagatay
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  2. Mehmet Ozturk
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Correspondence to Mehmet Ozturk.

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Cagatay, T., Ozturk, M. p53 mutation as a source of aberrant β-catenin accumulation in cancer cells. Oncogene 21, 7971–7980 (2002). https://doi.org/10.1038/sj.onc.1205919

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