P53 MUTATIONS IN COLORECTAL-CANCER
P53 MUTATIONS IN COLORECTAL-CANCER
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DOI：
10.1073/pnas.87.19.7555
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发表时间：
1990-10-01
影响因子：
11.1
通讯作者：
LANE, DP
中科院分区：
文献类型：
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作者：
RODRIGUES, NR;ROWAN, A;LANE, DP
用p53特异性抗体对原发性结肠直肠癌进行免疫组织学染色，结果表明，检查了50%的恶性肿瘤。良性腺瘤p53表达均为阴性。为了确定这种过度表达的分子基础，我们检测了10个结直肠癌细胞系中p53蛋白的表达。在ELISA、细胞染色和免疫沉淀研究中，6个细胞系表达高水平的p53。直接测序和化学错配切割分析的p53 cDNA，通过使用聚合酶链反应在这些细胞系中显示，所有的细胞系表达高水平的p53合成的mRNA编码突变型p53蛋白。在p53表达较低的四个细胞系中的两个中，仍然检测到点突变。因此，我们得出结论，p53的过度表达是突变的同义词，但有些突变不会被简单的免疫组化分析检测。p53基因突变是人类结直肠癌发展中最常见的遗传变化之一。
Immunohistological staining of primary colorectal carcinomas with antibodies specific to p53 demonstrated gross overexpression of the protein in .apprxeq. 50% of the malignant tumors examined. Benign adenomas were all negative for p53 overexpression. To determine the molecular basis for this overexpression we examined p53 protein expression in 10 colorectal cancer cell lines. Six of the cell lines expressed high levels of p53 in ELISA, cell-staining, and immunoprecipitation studies. Direct sequencing and chemical-mismatch-cleavage analysis of p53 cDNA by using the polymerase chain reaction in these cell lines showed that all cell lines expressed high levels of p53 were synthesizing mRNAs that encoded mutant p53 proteins. In two of those four cell lines where p53 expression was lower, point mutations were still detected. Thus, we conclude that overexpression of p53 is synonymous with mutation, but some mutations would not be detected by simple immunohistochemical analysis. Mutation of the p53 gene is one of the commonest genetic changes in the development of human colorectal cancer.