Skip Navigation


Carcinogenesis Advance Access first published online on April 13, 2007
This version published online on April 17, 2007
Carcinogenesis, doi:10.1093/carcin/bgm079
This Article
Right arrow Advance Access manuscript (PDF) Freely available
Right arrow All Versions of this Article:
28/9/1859    most recent
bgm079v2
bgm079v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Sun, D.
Right arrow Articles by Zhu, L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Sun, D.
Right arrow Articles by Zhu, L.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author 2007. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Loss of p27Kip1 enhances tumor progression in chronic hepatocyte injury-induced liver tumorigenesis with widely ranging effects on Cdk2 or Cdc2 activation

Daqian Sun1,2, Hao Ren1,2, Michael Oertel2, Rani S. Sellers3 and Liang Zhu1,2

1 Department of Developmental and Molecular Biology, Marion Bessin Liver Research Center and Albert Einstein Comprehensive Cancer Center, Albert Einstein College of Medicine, Bronx, NY 10461, USA
2 Department of Medicine, Marion Bessin Liver Research Center and Albert Einstein Comprehensive Cancer Center, Albert Einstein College of Medicine, Bronx, NY 10461, USA
3 Department of Pathology, Marion Bessin Liver Research Center and Albert Einstein Comprehensive Cancer Center, Albert Einstein College of Medicine, Bronx, NY 10461, USA

Corresponding author: Dr. Liang Zhu, Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Room U-521, Bronx, NY 10461, USA, Phone: 718-430-3320, Fax: 718-430-8975, Email: lizhu{at}aecom.yu.edu

Effects of p27Kip1 inactivation on tumorigenesis vary from promotion to prevention dependent on the mouse models used. When p27 inactivation has a positive effect on tumorigenesis, deregulated activation of Cdks is generally believed to be the underlying mechanism since the function of p27 as an inhibitor of Cdks is firmly established. Here, we determined the effects of p27 inactivation on disease progression and Cdk activation in mouse liver tumorigenesis that originates from hepatocyte regenerative proliferation in response to chronic liver injury, an established etiology in most human liver cancer. Our results show that inactivation of p27 did not affect early stage hepatocyte regenerative proliferation but promoted tumor cell proliferation and progression in the late stage of the disease. Interestingly, Cdc2 overexpression was observed in all and cyclin E1 was overexpressed in half of the late stage tumors regardless of p27 status; and p27 inactivation led to significant activation of Cdk2 or Cdc2 only in half of the p27-deficient tumors. These results reveal a tumor suppressor role of p27 in chronic hepatocyte injury-induced liver tumorigenesis and, at the same time, the need to further study the mechanisms for tumor promotion by p27 inactivation.

Key Words: p27Kip1 • HBV • liver tumor • Cdk2 • Cdc2 • cyclin E

The figures have been added in this version.

Received November 28, 2006; revised March 30, 2007; accepted April 2, 2007.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.