Expression of the p53 tumour suppressor gene product is a determinant of chemosensitivity.
Expression of the p53 tumour suppressor gene product is a determinant of chemosensitivity.
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p53 肿瘤抑制基因产物的表达是化疗敏感性的决定因素。
DOI：
10.1006/bbrc.1994.1223
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发表时间：
1994
影响因子：
3.1
通讯作者：
P. Andreotti
中科院分区：
文献类型：
--
作者：
R. Petty;I. Cree;L. Sutherland;E. Hunter;D. Lane;P. Preece;P. Andreotti
许多细胞毒性剂通过引起DNA损伤而起作用，并且已知p53肿瘤抑制基因参与对DNA损伤的细胞反应。由于p53的失活在许多肿瘤中很常见，我们想知道这是否会影响癌细胞对细胞毒性药物的敏感性。我们已经证明，这确实是在转化的小鼠细胞系与突变的p53基因和没有p53基因，p53“敲除”小鼠成纤维细胞，和正常的人皮肤成纤维细胞与反义p53寡核苷酸处理的情况。此外，我们已经证明了p53蛋白表达在人类乳腺癌标本和他们的化疗敏感性之间的相关性。结果表明，p53的失活或突变使细胞对那些主要作用机制是DNA损伤的细胞毒性药物更敏感。
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.