Expression of the p53 tumour suppressor gene product is a determinant of chemosensitivity

R. D. Petty, I. A. Cree, L. A. Sutherland, E. M. Hunter, D. P. Lane, P. E. Preece, P. E. Andreotti

    Research output: Contribution to journalArticle

    57 Citations (Scopus)

    Abstract

    Many cytotoxic agents act by causing DNA damage, and the p53 tumour suppressor gene is known to be involved in the cellular response to DNA damage. Since inactivation of p53 is common in many tumours, we wondered if this would affect the sensitivity of cancer cells to cytotoxic agents. We have shown that this is indeed the case in transformed mouse cell lines with and without a mutated p53 gene; p53 "knockout" mouse fibroblasts, and normal human skin fibroblasts treated with an anti-sense p53 oligonucleotide. In addition, we have demonstrated a correlation between p53 protein expression in human breast cancer specimens and their chemosensitivity. The results show that inactivation or mutation of p53 renders cells more sensitive to those cytotoxic drugs whose primary mechanism of action is DNA damage.

    Original languageEnglish
    Pages (from-to)264-270
    Number of pages7
    JournalBiochemical and Biophysical Research Communications
    Volume199
    Issue number1
    DOIs
    Publication statusPublished - 28 Feb 1994

    Fingerprint

    Tumor Suppressor Genes
    DNA Damage
    Tumors
    Genes
    Cytotoxins
    Fibroblasts
    DNA
    Cells
    Transformed Cell Line
    Antisense Oligonucleotides
    p53 Genes
    Knockout Mice
    Oligonucleotides
    Neoplasms
    Skin
    Breast Neoplasms
    Mutation
    Pharmaceutical Preparations
    Proteins

    Keywords

    • Animals
    • Antibiotics, Antineoplastic
    • Base Sequence
    • Cell Line
    • Gene Expression
    • Genes, p53
    • Humans
    • In Vitro Techniques
    • Mice
    • Mice, Knockout
    • Molecular Sequence Data
    • Oligonucleotides, Antisense
    • RNA, Messenger
    • Tumor Cells, Cultured
    • Tumor Suppressor Protein p53

    Cite this

    Petty, R. D. ; Cree, I. A. ; Sutherland, L. A. ; Hunter, E. M. ; Lane, D. P. ; Preece, P. E. ; Andreotti, P. E. / Expression of the p53 tumour suppressor gene product is a determinant of chemosensitivity. In: Biochemical and Biophysical Research Communications. 1994 ; Vol. 199, No. 1. pp. 264-270.
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    abstract = "Many cytotoxic agents act by causing DNA damage, and the p53 tumour suppressor gene is known to be involved in the cellular response to DNA damage. Since inactivation of p53 is common in many tumours, we wondered if this would affect the sensitivity of cancer cells to cytotoxic agents. We have shown that this is indeed the case in transformed mouse cell lines with and without a mutated p53 gene; p53 {"}knockout{"} mouse fibroblasts, and normal human skin fibroblasts treated with an anti-sense p53 oligonucleotide. In addition, we have demonstrated a correlation between p53 protein expression in human breast cancer specimens and their chemosensitivity. The results show that inactivation or mutation of p53 renders cells more sensitive to those cytotoxic drugs whose primary mechanism of action is DNA damage.",
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    Expression of the p53 tumour suppressor gene product is a determinant of chemosensitivity. / Petty, R. D.; Cree, I. A.; Sutherland, L. A.; Hunter, E. M.; Lane, D. P.; Preece, P. E.; Andreotti, P. E.

    In: Biochemical and Biophysical Research Communications, Vol. 199, No. 1, 28.02.1994, p. 264-270.

    Research output: Contribution to journalArticle

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    AU - Petty, R. D.

    AU - Cree, I. A.

    AU - Sutherland, L. A.

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    AU - Preece, P. E.

    AU - Andreotti, P. E.

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    KW - In Vitro Techniques

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    KW - Mice, Knockout

    KW - Molecular Sequence Data

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    KW - RNA, Messenger

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