Identification of a novel promoter and exons of the c-ERBB-2 gene
Identification of a novel promoter and exons of the c-ERBB-2 gene
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DOI：
10.1006/bbrc.1999.0634
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发表时间：
1999-05-19
影响因子：
3.1
通讯作者：
Terada, M
中科院分区：
文献类型：
--
作者：
Nezu, M;Sasaki, H;Terada, M
c-ERBB-2基因在各种癌症中经常扩增。在对扩增单位的结构表征的研究过程中，我们分离了四个cDNA克隆，A39，GRB 7，C51和CAB 1，其相应的基因定位在c-ERBB-2基因座上。在c-ERBB-2基因上游约12 kb处有一个暂定基因C51。通过克隆C51全长cDNA克隆和逆转录PCR（RT-PCR）方法，我们鉴定了一个新的c-ERBB-2转录本，其中含有新的5'端序列（包括C51序列），表明c-ERBB-2基因具有新的启动子和新的外显子。c-ERBB-2的新启动子和外显子的结构组织通过对含有前述c-ERBB-2基因的5 ′侧翼区的总大小约20 kb的基因组DNA克隆进行全序列分析而揭示。在乳腺癌细胞系MCF-7中瞬时表达新鉴定的启动子-报告基因构建体表明，负责启动子活性的元件包含在转录起始位点上游的697 bp区域中。新的转录物可以编码在胞外结构域的部分中不同的蛋白质。虽然预测的蛋白产物的存在没有检查，这份报告是重要的，因为它提供了一个新的方面的c-ERBB-2原癌基因的产品。(C)北京：科学出版社.
The c-ERBB-2 gene is frequently amplified in various cancers. During the course of studies on the structural characterization of the amplification units, we isolated four cDNA clones, A39, GRB7, C51 and CAB1 with corresponding genes localized on the c-ERBB-2 locus. A tentative gene, C51, was located at about 12 kb upstream of the c-ERBB-2 gene. By molecular cloning of a full-length cDNA clone of C51 and the reverse transcription PCR (RT-PCR) method, we identified a novel transcript of c-ERBB-2 containing new 5' sequences including the C51 sequence, demonstrating that the c-ERBB-2 gene has a novel promoter and new exons. The structural organization of the novel promoter and exons of c-ERBB-2 was revealed by complete sequence analysis of a total size of about 20 kb of genomic DNA clones containing the 5'-flanking region of the previously described c-ERBB-2 gene. Transient expression of the newly identified promoter-reporter gene constructs in breast cancer cell line MCF-7 showed that the elements responsible for promoter activity were contained in a 697 bp region upstream of the transcriptional start site. The new transcript may encode a protein different in the portion of the extracellular domain. Although the presence of the predicted protein product was not examined, this report is important in that it provides a new aspect of the c-ERBB-2 protooncogene products. (C) 1999 Academic Press.