Cited by 1,949Cancer-related Molecular PathwaysSarcoma Diagnosis and TreatmentHeat shock proteins research

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Amplification of a gene encoding a p53-associated protein in human sarcomas

Oliner, J. D., Kinzler, K. W., Meltzer, P. S., George, D. L., Vogelstein, B.·1992·Nature

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Abstract

Despite extensive data linking mutations in the p53 gene to human tumorigenesis, little is known about the cellular regulators and mediators of p53 function. MDM2 is a strong candidate for one such cellular protein; the MDM2 gene was originally identified by virtue of its amplification in a spontaneously transformed derivative of mouse BALB/c cells and the MDM2 protein subsequently shown to bind to p53 in rat cells transfected with p53 genes. To determine whether MDM2 plays a role in human cancer, we have cloned the human MDM2 gene. Here we show that recombinant-derived human MDM2 protein binds human p53 in vitro, and we use MDM2 clones to localize the human MDM2 gene to chromosome 12q13-14. Because this chromosomal position appears to be altered in many sarcomas, we looked for changes in human MDM2 in such cancers. The gene was amplified in over a third of 47 sarcomas, including common bone and soft tissue forms. These results are consistent with the hypothesis that MDM2 binds to p53, and that amplification of MDM2 in sarcomas leads to escape from p53-regulated growth control. This mechanism of tumorigenesis parallels that for virally-induced tumours, in which viral oncogene products bind to and functionally inactivate p53.

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Authors: Oliner, J. D., Kinzler, K. W., Meltzer, P. S., George, D. L., & Vogelstein, B.
Affiliations: University of Michigan (US)
Johns Hopkins University (US)
University of Pennsylvania (US)
ORCID: Oliner, J. D.
Kinzler, K. W.
Meltzer, P. S.
George, D. L.
Vogelstein, B.
Venue: Nature
Publisher: Springer Science and Business Media LLC
Published: 1992-07
Volume: 358
Issue: 6381
Pages: 80-83
ISSN: 0028-0836 (ISSN-L)
1476-4687
DOI: 10.1038/358080a0
OpenAlex: W2091151265
Cited by: 1,949
References: 32
Citations by year: 2026: 14 · 2025: 22 · 2024: 23 · 2023: 27 · 2022: 25 · 2021: 36 · 2020: 37 · 2019: 32 · 2018: 20 · 2017: 37 · 2016: 52 · 2015: 46 · 2014: 63 · 2013: 46 · 2012: 58
FWCI: 52.87
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
Locations: Nature (publishedVersion)
PubMed (publishedVersion)
Deep Blue (University of Michigan) (submittedVersion)
Topics: Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
Health Sciences › Medicine › Oncology › Sarcoma Diagnosis and Treatment
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heat shock proteins research
Keywords: MDM2, p53, gene amplification, sarcoma, p53 binding, tumor suppressor inactivation, bone sarcoma, soft tissue sarcoma, viral oncogenes, carcinogenesis
MeSH terms: Amino Acid Sequence, Base Sequence, Chromosomes, Human, Pair 12, Cloning, Molecular, DNA, Gene Amplification, Humans, Molecular Sequence Data, Neoplasm Proteins, Neoplasms, Nuclear Proteins, Proto-Oncogene Proteins, RNA, Messenger, RNA, Neoplasm, Sequence Homology, Nucleic Acid, Gene Expression, Tumor Suppressor Protein p53, Sequence Alignment, Proto-Oncogene Proteins c-mdm2

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Amplification of a gene encoding a p53-associated protein in human sarcomas

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