Tumor suppression and normal aging in mice with constitutively high p53 activity
Open accessAbstract
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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- Authors
- Mendrysa, S. M., O'Leary, K. A., McElwee, M. K., Michalowski, J., Eisenman, R. N., Powell, D. A., & Perry, M. E.
- Affiliations
- University of Wisconsin–Madison (US)
- University of Wisconsin System (US)
- National Institutes of Health (US)
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2006-01-01
- Volume
- 20
- Issue
- 1
- Pages
- 16-21
- ISSN
- 0890-9369 (ISSN-L)
- 1549-5477
- PMC
- PMC1356096
- OpenAlex
- W2113724972
- Cited by
- 210
- References
- 28
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 1 · 2023: 7 · 2022: 3 · 2021: 9 · 2020: 4 · 2019: 8 · 2018: 3 · 2017: 8 · 2016: 7 · 2015: 4 · 2014: 9 · 2013: 11 · 2012: 18
- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Genes & Development (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- American Cancer Society
- National Institutes of Health
- National Cancer Institute
- Topics
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Keywords
- p53, MDM2, tumor suppression, aging, lifespan, carcinogenesis, cancer therapy targets
- MeSH terms
- Aging, Animals, Bone and Bones, Intestinal Neoplasms, Leukocyte Count, Mice, Mutant Strains, Skin, Survival Rate, Tumor Suppressor Protein p53, Mice, Proto-Oncogene Proteins c-mdm2
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