PIN1 expression contributes to hepatic carcinogenesis

R. W. Pang, Kin Wah Lee, K. Man, R. T. Poon, S. T. Fan, Y. L. Kwong, E. Tse

Research output: Journal article publicationJournal articleAcademic researchpeer-review

56 Citations (Scopus)

Abstract

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.
Original languageEnglish
Pages (from-to)19-25
Number of pages7
JournalJournal of Pathology
Volume210
Issue number1
DOIs
Publication statusPublished - 1 Sep 2006
Externally publishedYes

Keywords

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

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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