Semba K, Kamata N, Toyoshima K, Yamamoto T
Proc Natl Acad Sci U S A. 1985 Oct;82(19):6497-501. doi: 10.1073/pnas.82.19.6497.
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 was 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, approximately 30-fold amplification of c-erbB-2 was observed in a human adenocarcinoma of the salivary gland.
从一个人类基因组文库中，我们获得了6个与v-erbB相关的DNA克隆。从其中一个克隆λ107制备的DNA探针，与人类DNA的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，这两个片段均未被扩增。此外，来自λ107的探针与一种单一的4.8千碱基的聚腺苷酸加尾RNA物种杂交，且不与表皮生长因子受体mRNA反应。因此，我们得出结论，克隆λ107代表一个与v-erbB相关的基因（c-erbB-2），它与表皮生长因子受体基因不同。相比之下，另外5个克隆被证明代表表皮生长因子受体基因（c-erbB-1）。对λ107插入片段的部分核苷酸序列分析表明，该克隆至少包含7个推定的外显子，其中6个外显子可编码src癌基因家族蛋白产物特有的激酶结构域。Southern印迹分析显示，大鼠c-erbB-2基因和大鼠neu癌基因的限制性酶切图谱非常相似，提示c-erbB-2可能参与人类癌症的发生。事实上，在一例人类涎腺腺癌中观察到c-erbB-2约30倍的扩增。
