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

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Department of Cell Biology

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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.

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

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

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