Genetic Mechanisms of Tumor Suppression by the Human p53 Gene

DOI Web Site 16 Citations
  • Phang-Lang Chen
    Department of Pathology and Center for Molecular Genetics, School of Medicine, University of California, San Diego, La Jolla 92093-0612.
  • Yumay Chen
    Department of Pathology and Center for Molecular Genetics, School of Medicine, University of California, San Diego, La Jolla 92093-0612.
  • Robert Bookstein
    Department of Pathology and Center for Molecular Genetics, School of Medicine, University of California, San Diego, La Jolla 92093-0612.
  • Wen-Hwa Lee
    Department of Pathology and Center for Molecular Genetics, School of Medicine, University of California, San Diego, La Jolla 92093-0612.

Abstract

<jats:p>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.</jats:p>

Journal

  • Science

    Science 250 (4987), 1576-1580, 1990-12-14

    American Association for the Advancement of Science (AAAS)

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