Tumorigenic potential associated with enhanced expression of a gene that is amplified in a mouse tumor cell line.
Open accessAbstract
We have carried out an analysis of amplified DNA sequences present in a tumorigenic mouse cell line, designated 3T3DM, to determine if the presence of cellular transforming activity is correlated with the elevated expression of any of the amplified genes. These studies utilized a selection protocol that allowed for DNA sequence amplification after the introduction of each gene into non-transformed recipient cells. Cell lines obtained from this selection protocol were assayed for tumorigenicity in nude mice. The results provided evidence that a gene, mdm2, that is amplified more than 50-fold in the 3T3DM cell line, induces tumorigenicity when experimentally overexpressed in NIH3T3 cells and in Rat2 cells. Analysis of the predicted amino acid composition of the mdm2 product(s) revealed features similar to those that have been shown to be functionally significant in certain DNA binding proteins/transcriptional activators. These include two potential metal binding motifs and a negatively charged domain rich in acidic amino acid residues. Overall, the data support the conclusion that mdm2 represents an evolutionarily conserved gene with tumorigenic potential and a predicted role in mechanisms of cellular growth control.
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Overexpression of Mdm2 has been demonstrated to be transforming.
“Mdm2 is considered an oncogene, as its overexpression has been demonstrated to be transforming (16).”
From Mdm2 Promotes Genetic Instability and Transformation Independent of p53 (2008) · cites this paper as [16]
Overexpression of MDM2 in immortalized mouse NIH3T3 cells renders them tumorigenic.
“By contrast, the overexpression of MDM2 in immortalized mouse NIH3T3 cells renders them tumorigenic62.”
From MDM2, MDMX and p53 in oncogenesis and cancer therapy (2013) · cites this paper as [62]
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- Authors
- Fakharzadeh, S. S., Trusko, S. P., & George, D. L.
- Affiliations
- University of Pennsylvania (US)
- Venue
- The EMBO Journal
- Published
- 1991-06-01
- Volume
- 10
- Issue
- 6
- Pages
- 1565-1569
- ISSN
- 0261-4189 (ISSN-L)
- 1460-2075
- PMC
- PMC452821
- OpenAlex
- W1576330810
- Cited by
- 704
- References
- 25
- Citations by year
- 2026: 4 · 2025: 4 · 2024: 9 · 2023: 9 · 2022: 7 · 2021: 8 · 2020: 13 · 2019: 13 · 2018: 10 · 2017: 16 · 2016: 20 · 2015: 10 · 2014: 20 · 2013: 24 · 2012: 21
- FWCI
- 11.71
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The EMBO Journal (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5p50gm032592-05)
- National Institute of General Medical Sciences (GM-07170, T32GM007170, GM-32592)
- Topics
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Health Sciences › Medicine › Pathology and Forensic Medicine › Cancer Mechanisms and Therapy
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
- Keywords
- MDM2, gene amplification, tumorigenicity, cell transformation, overexpression, nude mouse xenograft, NIH3T3 cells, metal-binding motifs, DNA-binding proteins, transcriptional activator, cell growth regulation, evolutionarily conserved genes
- MeSH terms
- Amino Acid Sequence, Animals, Base Sequence, Chromosome Mapping, Cloning, Molecular, DNA, Biological Evolution, Gene Amplification, Molecular Sequence Data, Neoplasm Proteins, Neoplasms, Experimental, Nuclear Proteins, Oncogenes, Proto-Oncogene Proteins, RNA, Neoplasm, Transfection, Tumor Cells, Cultured, Gene Expression Regulation, Neoplastic, Zinc Fingers, Mice, Proto-Oncogene Proteins c-mdm2
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