title: PIN1 overexpression and beta-catenin gene mutations are distinct oncogenic events in human hepatocellular carcinoma.
abstract: 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.
authors.affiliation: Department of Medicine, Division of Haematology/Oncology, University of Hong Kong, Queen Mary Hospital, Hong Kong.
authors.forename: Roberta
authors.initials: R
authors.lastname: Pang
authors.forename: John
authors.initials: J
authors.lastname: Yuen
authors.forename: Man Fung
authors.initials: MF
authors.lastname: Yuen
authors.forename: Ching Lung
authors.initials: CL
authors.lastname: Lai
authors.forename: Terence K W
authors.initials: TK
authors.lastname: Lee
authors.forename: Kwan
authors.initials: K
authors.lastname: Man
authors.forename: Ronnie T P
authors.initials: RT
authors.lastname: Poon
authors.forename: Sheung Tat
authors.initials: ST
authors.lastname: Fan
authors.forename: Chun M
authors.initials: CM
authors.lastname: Wong
authors.forename: Irene O L
authors.initials: IO
authors.lastname: Ng
authors.forename: Yok Lam
authors.initials: YL
authors.lastname: Kwong
authors.forename: Eric
authors.initials: E
authors.lastname: Tse
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000209:etiology / Q000235:genetics / Q000378:metabolism*; D019938:Cyclin D1 / Q000096:biosynthesis / Q000235:genetics; D003598:Cytoskeletal Proteins / Q000235:genetics*; D006801:Humans; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D019696:Peptidylprolyl Isomerase / Q000096:biosynthesis / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015534:Trans-Activators / Q000235:genetics*; D014162:Transfection; D051176:beta Catenin
chemical_list: C495270:CTNNB1 protein, human; D003598:Cytoskeletal Proteins; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D015534:Trans-Activators; D051176:beta Catenin; D019938:Cyclin D1; C000606846:PIN1 protein, human; D019696:Peptidylprolyl Isomerase