PREDISPOSITION TO NEOPLASTIC TRANSFORMATION CAUSED BY GENE REPLACEMENT OF H-RAS1
PREDISPOSITION TO NEOPLASTIC TRANSFORMATION CAUSED BY GENE REPLACEMENT OF H-RAS1
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DOI：
10.1126/science.8502998
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发表时间：
1993-06-04
期刊：
影响因子：
56.9
通讯作者：
BISHOP, JM
中科院分区：
文献类型：
--
作者：
FINNEY, RE;BISHOP, JM
使用同源重组将名义上的转化突变引入 Rat1 成纤维细胞的内源性 H-ras1 基因中。尽管突变体和剩余的正常等位基因均表达相同，但杂合细胞并未发生肿瘤转化。相反，自发转化的细胞以低频率从杂合子中产生，并且这些细胞中的大多数扩增了突变等位基因。因此，激活的H-ras1等位基因本身并不比正常等位基因占优势，而是使细胞易于通过独立事件（例如突变等位基因的扩增）进行转化。
Homologous recombination was used to introduce a nominally transforming mutation into an endogenous H-ras1 gene in Rat1 fibroblasts. Although both the mutant and the remaining normal allele were expressed equally, the heterozygous cells were not neoplastically transformed. Instead, spontaneously transformed cells arose from the heterozygotes at a low frequency, and the majority of these cells had amplified the mutant allele. Thus, the activated H-ras1 allele was not by itself dominant over the normal allele but predisposed cells to transformation by independent events, such as amplification of the mutant allele.