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

J. D. Oliner, Kenneth W Kinzler, P. S. Meitzer, D. L. George, Bert Vogelstein

Research output: Contribution to journalArticle

Abstract

DESPITE extensive data linking mutations in the p53 gene to human tumorigenesis1, 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 cells2 and the MDM2 protein subsequently shown to bind to p53 in rat cells transfected with p53 genes3,4. 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 sarcomas5,7, 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 tumours8,9, in which viral oncogene products bind to and functionally inactivate p53.

Original languageEnglish (US)
Pages (from-to)80-83
Number of pages4
JournalNature
Volume358
Issue number6381
StatePublished - Jul 2 1992

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Gene Amplification
Sarcoma
Proteins
Genes
Chromosomes, Human, Pair 14
Oncogene Proteins
p53 Genes
Neoplasms
Carcinogenesis
Clone Cells
Bone and Bones
Mutation
Growth

ASJC Scopus subject areas

  • General

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Amplification of a gene encoding a p53-associated protein in human sarcomas. / Oliner, J. D.; Kinzler, Kenneth W; Meitzer, P. S.; George, D. L.; Vogelstein, Bert.

In: Nature, Vol. 358, No. 6381, 02.07.1992, p. 80-83.

Research output: Contribution to journalArticle

Oliner, JD, Kinzler, KW, Meitzer, PS, George, DL & Vogelstein, B 1992, 'Amplification of a gene encoding a p53-associated protein in human sarcomas', Nature, vol. 358, no. 6381, pp. 80-83.
Oliner, J. D. ; Kinzler, Kenneth W ; Meitzer, P. S. ; George, D. L. ; Vogelstein, Bert. / Amplification of a gene encoding a p53-associated protein in human sarcomas. In: Nature. 1992 ; Vol. 358, No. 6381. pp. 80-83.
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