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Science 14 December 1990:
Vol. 250. no. 4987, pp. 1576 - 1580
DOI: 10.1126/science.2274789
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Articles

Science, Vol 250, Issue 4987, 1576-1580
Copyright © 1990 by American Association for the Advancement of Science

articles

Genetic mechanisms of tumor suppression by the human p53 gene

PL Chen, YM Chen, R Bookstein, and WH Lee

Department of Pathology, School of Medicine, University of California, San Diego, La Jolla 92093-0612.

Mutations of the gene encoding p53, a 53-kilodalton cellular protein, are found frequently in human tumor cells, suggesting a crucial role for this gene in human oncogenesis. To model the stepwise mutation or loss of both p53 alleles during tumorigenesis, a human osteosarcoma cell line, Saos-2, was used that completely lacked endogenous p53. Single copies of exogenous p53 genes were then introduced by infecting cells with recombinant retroviruses containing either point-mutated or wild-type versions of the p53 cDNA sequence. Expression of wild-type p53 suppressed the neoplastic phenotype of Saos-2 cells, whereas expression of mutated p53 conferred a limited growth advantage to cells in the absence of wild-type p53. Wild-type p53 was phenotypically dominant to mutated p53 in a two-allele configuration. These results suggest that, as with the retinoblastoma gene, mutation of both alleles of the p53 gene is essential for its role in oncogenesis.


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WT1-mediated growth suppression of Wilms tumor cells expressing a WT1 splicing variant.
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Wild-type p53 mediates positive regulation of gene expression through a specific DNA sequence element..
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Oncogenic forms of p53 inhibit p53-regulated gene expression.
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