PIN1 overexpression and β-catenin gene mutations are distinct oncogenic events in human hepatocellular carcinoma
- 5 April 2004
- journal article
- Published by Springer Nature in Oncogene
- Vol. 23 (23) , 4182-4186
- https://doi.org/10.1038/sj.onc.1207493
Abstract
The peptidyl-proplyl-isomerase, PIN1, upregulates -catenin by inhibiting its interaction with APC. -catenin accumulation occurs in about 70% of hepatocellular carcinoma (HCC), of which only 20% are due to -catenin mutations. The role of PIN1 in -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 -catenin accumulation, with 68% of cases showing concomitant -catenin and cyclin D1 accumulation. PIN1 was shown to contribute to -catenin and cyclin D1 overexpression directly by in vitro cell-line transfection experiments. Finally, we showed that PIN1 overexpression and -catenin gene mutations appeared to be mutually exclusive events, leading to -catenin accumulation in HCC. These results showed that PIN1 overexpression leading to -catenin accumulation might be a critical event in hepatocarcinogenesis, and that PIN1 is a potential target for therapeutic intervention in HCC.Keywords
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