Tumor suppression and normal aging in mice with constitutively high p53 activity.
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.
Mendrysa
Susan M
SM
Department of Oncology, University of Wisconsin, Madison, 53706, USA.
O'Leary
Kathleen A
KA
McElwee
Matthew K
MK
Michalowski
Jennifer
J
Eisenman
Robert N
RN
Powell
Douglas A
DA
Perry
Mary Ellen
ME
D000375:Aging / Q000378:metabolism*; D000818:Animals; D001842:Bone and Bones / Q000378:metabolism / Q000473:pathology; D007414:Intestinal Neoplasms / Q000378:metabolism / Q000473:pathology*; D007958:Leukocyte Count; D051379:Mice; D008817:Mice, Mutant Strains; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics / Q000378:metabolism*; D012867:Skin / Q000378:metabolism / Q000473:pathology; D015996:Survival Rate; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
D016159:Tumor Suppressor Protein p53; C497207:Mdm2 protein, mouse; D051736:Proto-Oncogene Proteins c-mdm2