Bremner R, Balmain A
Beatson Institute for Cancer Research, Bearsden, Glasgow, Scotland.
Cell. 1990 May 4;61(3):407-17. doi: 10.1016/0092-8674(90)90523-h.
Initiation of tumorigenesis in mouse skin can be accomplished by mutagenesis of the H-ras gene by treatment with chemical carcinogens. A mouse model system has been developed to study the additional genetic events that take place during tumor progression. Skin carcinomas were induced in F1 hybrid mice exhibiting restriction fragment length polymorphisms at multiple chromosomal loci. Analysis of loss of heterozygosity in such tumors showed that imbalance of alleles on mouse chromosome 7, on which the H-ras gene is located, occurs very frequently in skin carcinomas. The chromosomal alterations detected, which included both nondisjunction and mitotic recombination events, were only seen in tumors that have activated ras genes. We conclude that gross chromosomal alterations that elevate the copy number of mutant H-ras and/or lead to loss of normal H-ras are a consistent feature of mouse skin tumor development.
通过化学致癌物处理使H-ras基因发生突变，可引发小鼠皮肤肿瘤的形成。现已开发出一种小鼠模型系统，用于研究肿瘤进展过程中发生的其他遗传事件。在多个染色体位点表现出限制性片段长度多态性的F1杂交小鼠中诱导出皮肤癌。对此类肿瘤杂合性缺失的分析表明，H-ras基因所在的小鼠7号染色体上的等位基因失衡在皮肤癌中非常常见。检测到的染色体改变，包括不分离和有丝分裂重组事件，仅在已激活ras基因的肿瘤中出现。我们得出结论，导致突变型H-ras拷贝数增加和/或导致正常H-ras缺失的染色体大片段改变是小鼠皮肤肿瘤发展的一个持续特征。
