PIN1 overexpression and beta-catenin gene mutations are distinct oncogenic events in human hepatocellular carcinoma

Oncogene. 2004 May 20;23(23):4182-6. doi: 10.1038/sj.onc.1207493.


The peptidyl-proplyl-isomerase, PIN1, upregulates beta-catenin by inhibiting its interaction with APC. beta-catenin accumulation occurs in about 70% of hepatocellular carcinoma (HCC), of which only 20% are due to beta-catenin mutations. The role of PIN1 in beta-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 beta-catenin accumulation, with 68% of cases showing concomitant beta-catenin and cyclin D1 accumulation. PIN1 was shown to contribute to beta-catenin and cyclin D1 overexpression directly by in vitro cell-line transfection experiments. Finally, we showed that PIN1 overexpression and beta-catenin gene mutations appeared to be mutually exclusive events, leading to beta-catenin accumulation in HCC. These results showed that PIN1 overexpression leading to beta-catenin accumulation might be a critical event in hepatocarcinogenesis, and that PIN1 is a potential target for therapeutic intervention in HCC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Hepatocellular / etiology
  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / metabolism*
  • Cyclin D1 / biosynthesis
  • Cyclin D1 / genetics
  • Cytoskeletal Proteins / genetics*
  • Humans
  • NIMA-Interacting Peptidylprolyl Isomerase
  • Peptidylprolyl Isomerase / biosynthesis
  • Peptidylprolyl Isomerase / genetics*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Trans-Activators / genetics*
  • Transfection
  • beta Catenin


  • CTNNB1 protein, human
  • Cytoskeletal Proteins
  • NIMA-Interacting Peptidylprolyl Isomerase
  • Trans-Activators
  • beta Catenin
  • Cyclin D1
  • PIN1 protein, human
  • Peptidylprolyl Isomerase