PIN1 overexpression and beta-catenin gene mutations are distinct oncogenic events in human hepatocellular carcinoma.
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.
Pang
Roberta
R
Department of Medicine, Division of Haematology/Oncology, University of Hong Kong, Queen Mary Hospital, Hong Kong.
Yuen
John
J
Yuen
Man Fung
MF
Lai
Ching Lung
CL
Lee
Terence K W
TK
Man
Kwan
K
Poon
Ronnie T P
RT
Fan
Sheung Tat
ST
Wong
Chun M
CM
Ng
Irene O L
IO
Kwong
Yok Lam
YL
Tse
Eric
E
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
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