Abstract
The peptidyl-proplyl-isomerase, PIN1, upregulates β-catenin by inhibiting its interaction with APC. β-catenin accumulation occurs in about 70% of hepatocellular carcinoma (HCC), of which only 20% are due to β-catenin mutations. The role of PIN1 in β-catenin upregulation in HCC was investigated. PIN1 was shown to be overexpressed in more than 50% of HCC. All cases with PIN1 overexpression also showed β-catenin accumulation, with 68% of cases showing concomitant β-catenin and cyclin D1 accumulation. PIN1 was shown to contribute to β-catenin and cyclin D1 overexpression directly by in vitro cell-line transfection experiments. Finally, we showed that PIN1 overexpression and β-catenin gene mutations appeared to be mutually exclusive events, leading to β-catenin accumulation in HCC. These results showed that PIN1 overexpression leading to β-catenin accumulation might be a critical event in hepatocarcinogenesis, and that PIN1 is a potential target for therapeutic intervention in HCC.
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Acknowledgements
We thank Dr J Liang at the National Institute of Health, USA for providing the albumin promoter plasmid and Dr J Roy-Chowdhury at Albert Einstein College of Medicine, USA for providing the nontumorigenic liver cell line. This work was supported by a grant from Kadoorie Charitable Foundation, Hong Kong to YLK.
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Pang, R., Yuen, J., Yuen, M. et al. PIN1 overexpression and β-catenin gene mutations are distinct oncogenic events in human hepatocellular carcinoma. Oncogene 23, 4182–4186 (2004). https://doi.org/10.1038/sj.onc.1207493
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DOI: https://doi.org/10.1038/sj.onc.1207493
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