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PMID: 8417333 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

The mdm-2 oncogene can overcome wild-type p53 suppression of transformed cell growth.

Molecular and cellular biology ·Vol. 13 ·No. 1 ·1993-01-00 ·Pages 301-6

Finlay CA

Abstract

Expression of a p53-associated protein, Mdm-2 (murine double minute-2), can inhibit p53-mediated transactivation. In this study, overexpression of the Mdm-2 protein was found to result in the immortalization of primary rat embryo fibroblasts (REFs) and, in conjunction with an activated ras gene, in the transformation of REFs. The effect of wild-type p53 on the transforming properties of mdm-2 was determined by transfecting REFs with ras, mdm-2, and normal p53 genes. Transfection with ras plus mdm-2 plus wild-type p53 resulted in a 50% reduction in the number of transformed foci (relative to the level for ras plus mdm-2); however, more than half (9 of 17) of the cell lines derived from these foci expressed low levels of a murine p53 protein with the characteristics of a wild-type p53. These results are in contrast to previous studies which demonstrated that even minimal levels of wild-type p53 are not tolerated in cells transformed by ras plus myc, E1A, or mutant p53. The mdm-2 oncogene can overcome the previously demonstrated growth-suppressive properties of p53.

Related Genes
mdm-2 ras
MeSH Terms
Animals Cell Division Cell Transformation, Neoplastic/pathology Genes, Tumor Suppressor Neoplasm Proteins/pharmacology Nuclear Proteins Oncogene Proteins/genetics,immunology Precipitin Tests Proto-Oncogene Proteins/genetics,immunology Proto-Oncogene Proteins c-mdm2 Proto-Oncogenes Rats Rats, Inbred F344 Tumor Suppressor Protein p53/genetics
Chemicals
Neoplasm Proteins Nuclear Proteins Oncogene Proteins Proto-Oncogene Proteins Tumor Suppressor Protein p53 Mdm2 protein, rat Proto-Oncogene Proteins c-mdm2
Authors & Affiliations
1 authors, click to expand affiliations / ORCID
Finlay C A
Department of Molecular Biology, Princeton University, New Jersey 08544-1014.
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/mcb.13.1.301-306.1993
Published
1993-01-00
Pages
301-6
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC358909
Subset
IM
Grants
NCI NIH HHS · R01 CA55036 · United States
External Links
PubMed source DOI: 10.1128/mcb.13.1.301-306.1993 PMC Full Text View journal details
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