Tumor suppression and normal aging in mice with constitutively high p53 activity

Susan M. Mendrysa, Kathleen A. O'Leary, Matthew K. McElwee, Jennifer Michalowski, Robert N. Eisenman, Douglas A. Powell, Mary Ellen Perry

Research output: Contribution to journalArticlepeer-review

166 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)16-21
Number of pages6
JournalGenes and Development
Volume20
Issue number1
DOIs
StatePublished - Jan 1 2006

Keywords

  • Aging
  • Apoptosis
  • Cancer therapy
  • Mdm2
  • Tumor suppression
  • p53

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