Overexpression of Mdm2 in mice reveals a p53-independent role for Mdm2 in tumorigenesis

UMMS Affiliation

Department of Cell Biology

Publication Date


Document Type



Animals; *Cell Transformation, Neoplastic; Chimera; Crosses, Genetic; Female; Gene Deletion; *Genes, p53; Heterozygote; Humans; Male; Mice; Mice, Inbred C57BL; Mice, Inbred Strains; Mice, Transgenic; Neoplasm Proteins; Neoplasms, Experimental; *Nuclear Proteins; Promoter Regions (Genetics); Proto-Oncogene Proteins; Proto-Oncogene Proteins c-mdm2; Transcription, Genetic; Tumor Suppressor Protein p53


Life Sciences | Medicine and Health Sciences


The Mdm2 proto-oncogene is amplified to high copy numbers in human sarcomas and is overexpressed in a wide variety of other human cancers. Because Mdm2 protein forms a complex with the p53 tumor suppressor protein and down-regulates p53 function, the oncogenic potential of Mdm2 is presumed to be p53-dependent. To model these conditions in mice, we have used the entire Mdm2 gene, under transcriptional control of its native promoter region, as a transgene to create mice that overexpress Mdm2. The transgenic mice are predisposed to spontaneous tumor formation, and the incidence of sarcomas observed in the Mdm2-transgenic mice in the presence or absence of functional p53 demonstrates that, in addition to Mdm2-mediated inactivation of p53, there exists a p53-independent role for Mdm2 in tumorigenesis.


Proc Natl Acad Sci U S A. 1998 Dec 22;95(26):15608-12.

Journal/Book/Conference Title

Proceedings of the National Academy of Sciences of the United States of America

Related Resources

Link to Article in PubMed

PubMed ID


This document is currently not available here.