PIN1 expression contributes to hepatic carcinogenesis
Article first published online: 14 JUL 2006
Copyright © 2006 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
The Journal of Pathology
Volume 210, Issue 1, pages 19–25, September 2006
How to Cite
Pang, R., Lee, T., Man, K., Poon, R., Fan, S.-T., Kwong, Y.-L. and Tse, E. (2006), PIN1 expression contributes to hepatic carcinogenesis. J. Pathol., 210: 19–25. doi: 10.1002/path.2024
- Issue published online: 7 AUG 2006
- Article first published online: 14 JUL 2006
- Manuscript Accepted: 12 MAY 2006
- Manuscript Revised: 29 MAR 2006
- Manuscript Received: 28 FEB 2006
- Kadoorie Charitable Foundation
- RNA interference;
- hepatocellular carcinoma
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 β-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 β-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. Copyright © 2006 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.