AMPLIFICATION AND ENHANCED EXPRESSION OF THE EPIDERMAL GROWTH-FACTOR RECEPTOR GENE IN A431 HUMAN CARCINOMA-CELLS
AMPLIFICATION AND ENHANCED EXPRESSION OF THE EPIDERMAL GROWTH-FACTOR RECEPTOR GENE IN A431 HUMAN CARCINOMA-CELLS
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DOI：
10.1126/science.6200934
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发表时间：
1984-01-01
期刊：
影响因子：
56.9
通讯作者：
PASTAN, I
中科院分区：
文献类型：
--
作者：
MERLINO, GT;XU, YH;PASTAN, I
人表皮生长因子（EGF）受体的序列显示出与禽成红细胞增多症病毒v-er B B癌基因的高度同源性，这提高了该受体基因与c-er B B原癌基因相同的可能性。人A431表皮样癌细胞，其中有一个异常高的EGF受体数量，进行了检查，以确定是否EGF受体水平升高与基因扩增相关。用先前从A431互补DNA文库中分离的v-er B B基因片段或人EGF受体互补DNA克隆（pE 7）探测来自A431和其它人细胞系的基因组DNA的Southern印迹。当使用任一探针分析EcoRI或HindIII产生的DNA片段时，EGF受体DNA序列在A431中扩增约30倍。A431 DNA片段相对于正常成纤维细胞DNA的带型差异表明受体基因区域发生重排。A431细胞含有特征性的、突出的2.9-腺苷酸酶RNA。支持的假设，在A431细胞，基因扩增，可能与易位事件，可能会导致过度生产的EGF受体蛋白或外观的转化表型（或两者）。
The sequence of the human epidermal growth factor (EGF) receptor shows great homology with the avian erythroblastosis virus v-erb B oncogene, raising the possibility that the receptor gene is identical to the c-erb B protooncogene. Human A431 epidermoid carcinoma cells, which have an unusually high number of EGF receptors, were examined to determine whether elevated EGF receptor levels correlate with gene amplification. Southern blots of genomic DNA from A431 and other human cell lines were probed with either a v-erb B gene fragment or a human EGF receptor complementary DNA clone (pE7), previously isolated from an A431 complementary DNA library. When either probe was used to analyze EcoRI- or HindIII-generated DNA fragments, EGF receptor DNA sequences were amplified about 30-fold in A431. Differences in the banding pattern of A431 DNA fragments relative to normal fibroblast DNA indicate the occurrence of a rearrangement in the region of the receptor gene. The A431 cells contain a characteristic, prominent 2.9-kilobase RNA. The hypothesis is supported that, in A431 cells, gene amplification, possibly associated with a translocation event, may result in the overproduction of EGF receptor protein or the appearance of the transformed phenotype (or both).