P53 MUTATIONS ARE ABSENT FROM CARCINOGEN-INDUCED MOUSE-LIVER TUMORS BUT OCCUR IN CELL-LINES ESTABLISHED FROM THESE TUMORS
P53 MUTATIONS ARE ABSENT FROM CARCINOGEN-INDUCED MOUSE-LIVER TUMORS BUT OCCUR IN CELL-LINES ESTABLISHED FROM THESE TUMORS
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DOI：
10.1002/mc.2940060210
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发表时间：
1992-01-01
影响因子：
4.6
通讯作者：
SCHWARZ, M
中科院分区：
文献类型：
--
作者：
KRESS, S;KONIG, J;SCHWARZ, M
p53基因突变是人类肝细胞癌中常见的遗传学改变。我们已经研究了，通过聚合酶链反应产物的单链构象多态性分析，共93个致癌剂诱导的肝肿瘤小鼠三个不同的品系（C3 H/He，C57 BL/6 J，和B6 C3 F1）的存在下，p53畸变。从12个肝肿瘤建立的肝癌细胞系也包括在分析中。虽然p53基因的结构畸变没有检测到任何的主要小鼠肝肿瘤分析，单碱基置换发生在不同的位置内的p53基因在三个细胞系在体外繁殖。一个肝癌细胞系在不同的等位基因上携带两个点突变。所有四个突变都是G：C -> C：G或C：G -> G：C颠换。C3 H/He和B6 C3 F1小鼠原发性肝肿瘤中常见的c-Ha-ras基因第61位密码子突变在肝癌细胞系中未检测到。我们的数据表明（i）c-Ha-ras而不是p53突变在小鼠肝癌发生的早期阶段起重要作用;（ii）p53突变赋予突变的肝癌细胞体外选择性生长优势。
Mutations in the p53 gene are frequent genetic alterations in human hepatocellular carcinomas. We have examined, by single-strand conformation polymorphism analysis of polymerase chain reaction products, a total of 93 carcinogen-induced liver tumors from mice of three different strains (C3H/He, C57BL/6J, and B6C3F1) for the presence of p53 aberrations. Hepatoma lines, established from 12 liver tumors, were also included in the analysis. While structural aberrations of the p53 gene were not detected in any of the primary mouse liver tumors analyzed, single-base substitutions occurred at different locations within the p53 gene in three of the cell lines during in vitro propagation. One hepatoma line carried two point mutations on separate alleles. All four mutations were either G:C --> C:G or C:G --> G:C transversions. Mutations at codon 61 of the c-Ha-ras gene, which were frequent in primary liver tumors from C3H/He and B6C3F1 mice, were not detected in the hepatoma lines. Our data indicate (i) that c-Ha-ras but not p53 mutations play an important role during the early stages of mouse hepatocarcinogenesis and (ii) that p53 mutations confer a selective growth advantage to the mutated hepatoma cells in vitro.