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 accumnlation. 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.
Original language | English |
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Pages (from-to) | 4182-4186 |
Number of pages | 5 |
Journal | Oncogene |
Volume | 23 |
Issue number | 23 |
DOIs | |
Publication status | Published - 20 May 2004 |
Externally published | Yes |
Keywords
- β-catenin
- Hepatocellular carcinoma
- Peptidyl-prolyl-isomerase
- PIN1
ASJC Scopus subject areas
- Molecular Biology
- Genetics
- Cancer Research