PIN1 expression contributes to hepatic carcinogenesis.
The phospho-Ser/Thr-Pro specific prolyl-isomerase PIN1 is over-expressed in more than 50% of hepatocellular carcinomas (HCCs). To investigate its potential oncogenicity, we over-expressed PIN1 in a non-transformed human liver cell line MIHA. This resulted in up-regulation of beta-catenin and cyclin D1, leading to anchorage-independent growth in soft agar and tumorigenicity in nude mice. To further validate the role of PIN1 in hepatocarcinogenesis, PIN was suppressed by RNA interference (siRNA) in the HCC cell line PLC/PRF/5. siRNA-PIN1 transfection of PLC/PRF/5 cells led to repression of PIN1 expression, resulting in decreased levels of beta-catenin and cyclin D1. siRNA-PIN1 transfectants showed lower cell proliferation rates, reduced colony formation, and retarded cell cycle progression, with an increase in cells residing in G0/G1. Furthermore, soft agar colony formation was depressed, and tumorigenicity in nude mice was abrogated. These findings implicate PIN1 expression as an important step in hepatic carcinogenesis.
Pang
R W
RW
Department of Medicine, University of Hong Kong, Queen Mary Hospital, Pokfulam Road, Hong Kong.
Lee
T K
TK
Man
K
K
Poon
R T
RT
Fan
S-T
ST
Kwong
Y-L
YL
Tse
E
E
D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000235:genetics*; D002460:Cell Line; D045744:Cell Line, Tumor; D019938:Cyclin D1 / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics*; D051379:Mice; D008819:Mice, Nude; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D009363:Neoplasm Proteins / Q000235:genetics*; D019696:Peptidylprolyl Isomerase / Q000235:genetics*; D034622:RNA Interference; D012334:RNA, Neoplasm / Q000235:genetics; D014162:Transfection / Q000379:methods; D015854:Up-Regulation / Q000235:genetics; D051176:beta Catenin / Q000235:genetics
D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D009363:Neoplasm Proteins; D012334:RNA, Neoplasm; D051176:beta Catenin; D019938:Cyclin D1; C000606846:PIN1 protein, human; D019696:Peptidylprolyl Isomerase; C000606850:Pin1 protein, mouse