A V-ERBB-RELATED PROTOONCOGENE, C-ERBB-2, IS DISTINCT FROM THE C-ERBB-1/EPIDERMAL GROWTH FACTOR-RECEPTOR GENE AND IS AMPLIFIED IN A HUMAN SALIVARY-GLAND ADENOCARCINOMA

A V-ERBB-RELATED PROTOONCOGENE, C-ERBB-2, IS DISTINCT FROM THE C-ERBB-1/EPIDERMAL GROWTH FACTOR-RECEPTOR GENE AND IS AMPLIFIED IN A HUMAN SALIVARY-GLAND ADENOCARCINOMA
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DOI:
10.1073/pnas.82.19.6497
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发表时间:
1985-01-01
影响因子:
11.1
通讯作者:
YAMAMOTO, T
YAMAMOTO, T
中科院分区:
综合性期刊1区
文献类型:
--
作者:
SEMBA, K;KAMATA, N;YAMAMOTO, T

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从人类基因组文库中,我们获得了6个与v- erbb相关的DNA克隆。从其中一个克隆体。lambda中提取的DNA探针。107,与人类DNA 6.4和13千碱基对的EcoRI片段杂交。在编码表皮生长因子受体的基因被扩增的A431外阴癌细胞中,这两个片段都没有被扩增。此外,从.lambda。107只与4.8千碱基poly(a)+ RNA杂交,不与EGF受体mRNA发生反应。因此,我们得出结论,克隆.lambda。107表示与EGF受体基因不同的v- erbb相关基因(c-erbB-2)。相比之下,其他五个克隆被证明代表EGF受体基因(c-erbB-1)。.lambda的部分核苷酸序列分析。107 insert显示该克隆包含至少7个推测的外显子,其中6个可以编码SRC癌基因家族蛋白产物的激酶结构域特征。Southern blot分析显示,大鼠c-erbB-2基因的限制性模式与大鼠新致癌基因非常相似,提示c-erbB-2可能参与人类癌症。实际上,.apprxeq。c-erbB-2在人唾液腺腺癌中扩增30倍。
From a human genomic library, we obtained six v-erbB-related DNA clones. A DNA probe prepared from one of the clones, .lambda.107, hybridized to EcoRI fragments of 6.4 and 13 kilobase pairs of human DNA. Neither of these fragments were amplified in A431 vulva carcinoma cells, in which the gene encoding the epidermal growth factor receptor is amplified. In addition, the probe from .lambda.107 hybridized with a single, 4.8-kilobase poly(A)+ RNA species and did not react with EGF receptor mRNA. Thus, we conclude that clone .lambda.107 represents a v-erbB-related gene (c-erbB-2) that is distinct from the EGF receptor gene. In contrast, the other five clones were shown to represent the EGF receptor gene (c-erbB-1). Partial nucleotide sequence analysis of the .lambda.107 insert showed that this clone contained at least seven putative exons and that six of them could encode the kinase domain characteristic of protein products of the src oncogene family. Southern blot analysis showed close similarity of the restriction patterns of the rat c-erbB-2 gene and the rat neu oncogene, suggesting possible involvement of c-erbB-2 in human cancer. In fact, .apprxeq. 30-fold amplification of c-erbB-2 was observed in a human adenocarcinoma of the salivary gland.