Tumor suppression and normal aging in mice with constitutively high p53 activity
- Susan M. Mendrysa1,2,5,6,
- Kathleen A. O'Leary1,5,7,
- Matthew K. McElwee1,8,
- Jennifer Michalowski1,9,
- Robert N. Eisenman2,
- Douglas A. Powell3, and
- Mary Ellen Perry1,4,10
- 1Department of Oncology, University of Wisconsin, Madison, Wisconsin 53706, USA; 2Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA; 3Data Management Services, National Cancer Institute, Frederick, Maryland 21702, USA; 4Laboratory of Protein Dynamics and Signaling, National Cancer Institute, Frederick, Maryland 21702, USA
Abstract
The p53 inhibitor murine double-minute gene 2 (Mdm2) is a target for potential cancer therapies, however increased p53 function can be lethal. To directly address whether reduced Mdm2 function can inhibit tumorigenesis without causing detrimental side effects, we exploited a hypomorphic murine allele of mdm2 to compare the effects of decreased levels of Mdm2 and hence increased p53 activity on tumorigenesis and life span in mice. Here we report that mice with decreased levels of Mdm2 are resistant to tumor formation yet do not age prematurely, supporting the notion that Mdm2 is a promising target for cancer therapeutics.
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Footnotes
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Article and publication are at http://www.genesdev.org/cgi/doi/10.1101/gad.1378506.
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↵5 These authors contributed equally to this work.
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↵6 Present address: Department of Basic Medical Sciences, Purdue University, West Lafayette, IN 47907, USA;
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↵7 Present address: Department of Comparative Biosciences, University of Wisconsin, Madison, WI 53706, USA;
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↵8 Present address: Integrated Toxicology Program, Duke University, Durham, NC 27708, USA;
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↵9 Present address: Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA;
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↵10 Corresponding author.
↵10 E-MAIL perryma{at}mail.nih.gov; FAX (301) 402-1037.
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- Accepted November 2, 2005.
- Received September 23, 2005.
- Cold Spring Harbor Laboratory Press
