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

Roberta Pang, John Yuen, Man Fung Yuen, Ching Lung Lai, Kin Wah Lee, Kwan Man, Ronnie T.P. Poon, Sheung Tat Fan, Chun M. Wong, Irene O.L. Ng, Yok Lam Kwong, Eric Tse

Research output: Journal article publicationJournal articleAcademic researchpeer-review

96 Citations (Scopus)

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 languageEnglish
Pages (from-to)4182-4186
Number of pages5
JournalOncogene
Volume23
Issue number23
DOIs
Publication statusPublished - 20 May 2004
Externally publishedYes

Keywords

  • β-catenin
  • Hepatocellular carcinoma
  • Peptidyl-prolyl-isomerase
  • PIN1

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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