Display Settings:

Format

Send to:

Choose Destination
Oncogene. 2009 Dec 10;28(49):4344-52. doi: 10.1038/onc.2009.286.

Genetic inactivation of ApoJ/clusterin: effects on prostate tumourigenesis and metastatic spread.

Author information

  • 1Department of Experimental Medicine, University of Parma, Via Volturno 39, 43100 Parma, Italy. saverio.bettuzzi@unipr.it

Abstract

ApoJ/Clusterin (CLU) is a heterodimeric protein localized in the nucleus, cytoplasm or secretory organelles and involved in cell survival and neoplastic transformation. Its function in human cancer is still highly controversial. In this study, we examined the prostate of mice in which CLU has been genetically inactivated. Surprisingly, we observed transformation of the prostate epithelium in the majority of CLU knockout mice. Either PIN (prostate intraepithelial neoplasia) or differentiated carcinoma was observed in 100 and 87% of mice with homozygous or heterozygous deletion of CLU, respectively. Crossing CLU knockout with TRAMP (prostate cancer prone) mice results in a strong enhancement of metastatic spread. Finally, CLU depletion causes tumourigenesis in female TRAMP mice, which are normally cancer free. Mechanistically, deletion of CLU induces activation of nuclear factor-kB, a potentially oncogenic transcription factor important for the proliferation and survival of prostate cells.

PMID:
19784068
[PubMed - indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Icon for Nature Publishing Group
    Loading ...
    Write to the Help Desk