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Cytotoxic Drug Resistance Mechanisms pp 179–199Cite as

Analysis of the p53 Status of Tumors

An Overview of Methods

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Part of the book series: Methods in Molecular Medicine™ ((MIMM,volume 28))

Abstract

The tumor suppressor gene TP53, encoding the p53 protein, has its gene locus on the short arm of chromosome 17 p13.1 (1,2). p53 has been denoted “guardian of the genome” (3) owing to its essential cellular functions in apoptosis control, cell-cycle control, chromosomal segregation, gene transcription, and genomic stability (4). The gene encodes a protein of 393 amino acids (5). The tertiary structure of the p53 protein is known to a relatively large extent; the DNA binding region has been localized to amino acids 102 to 292. Murine double minute-2 (MDM2) binds to the amino terminal of the p53 protein and is a negative regulator of p53 (6). p53 is normally activated by ultraviolet (UV)-light, radiation, cytostatics, and carcinogens. The activation by these may involve interaction with the ataxia telangiectasia gene (ATM). The p53 gene can be inactivated by somatic or germ-line mutations. Somatic mutations in the p53 gene is the most common genetic abnormality so far described in human cancer (7). Patients with germ-line p53 mutation’s are part of the Li-Fraumeni syndrome. These patients have an increased risk of developing adrenocortical, breast, gastrointestinal tract, and lung carcinoma, as well as soft-tissue sarcoma and malignant melanoma (8,9). Studies on mice have revealed that induced deficiency of both alleles of the p53 gene is associated within an increased risk of lymphomas and sarcomas (10). p53 can also be inactivated by certain viral oncoproteins, such as human papilloma virus protein E6, SV40 large T-antigen, hepatitis B viral X protein, and adenovirus protein E1B (4).

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Authors and Affiliations

  1. Department of Oncology, University Hospital, Uppsala, Sweden

    Jonas Bergh

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  1. Jonas Bergh
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Editors and Affiliations

  1. University of Glasgow, Glasgow, UK

    Robert Brown

  2. BioMedEx, Killearn, UK

    Uta Böger-Brown

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© 1999 Humana Press Inc.

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Bergh, J. (1999). Analysis of the p53 Status of Tumors. In: Brown, R., Böger-Brown, U. (eds) Cytotoxic Drug Resistance Mechanisms. Methods in Molecular Medicine™, vol 28. Humana Press. https://doi.org/10.1385/1-59259-687-8:179

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  • DOI: https://doi.org/10.1385/1-59259-687-8:179

  • Publisher Name: Humana Press

  • Print ISBN: 978-0-89603-603-1

  • Online ISBN: 978-1-59259-687-4

  • eBook Packages: Springer Protocols

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