EGP-2, also known as Ep-CAM, is expressed at high levels on the surface of most carcinomas and is therefore considered an attractive target for anticancer strategies. To explore the mechanisms regulating the expression of EGP-2, sequences 3.4 kb upstream of the transcription start site were isolated and assayed for their ability to control the expression of the EGP-2 cDNA, the green fluorescent protein, the luciferase reporter gene and the thymidine kinase and cytosine deaminase suicide genes. Expression of these chimeric constructs as assessed in a range of different cell lines was restricted to cell lines expressing EGP-2. In addition, only cells expressing EGP-2 were sensitive for gancyclovir after being transiently transfected with EGP-2 promoter-driven thymidine kinase. Deletion analyses defined 687 bp upstream as the basic proximal promoter region, which could confer epithelial-specific expression to the GFP reporter gene in vitro. As these EGP-2 sequences can confer promoter activity to reporter and suicide genes in an EGP-2 restricted manner, they may be useful for gene therapy of EGP-2 expressing carcinomas.

中文翻译：

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EGP-2 / Ep-CAM启动子在癌衍生细胞系中靶向表达异源基因的用途。

EGP-2，也称为Ep-CAM，在大多数癌症的表面高水平表达，因此被认为是抗癌策略的诱人靶标。为了探索调节EGP-2表达的机制，分离了转录起始位点上游3.4 kb的序列，并分析了其控制EGP-2 cDNA，绿色荧光蛋白，荧光素酶报道基因和EGP-2表达的能力。胸苷激酶和胞嘧啶脱氨酶自杀基因。在一系列不同的细胞系中评估的这些嵌合构建体的表达限于表达EGP-2的细胞系。此外，只有表达EGP-2的细胞在被EGP-2启动子驱动的胸苷激酶瞬时转染后，对更昔洛韦敏感。缺失分析将上游687 bp定义为基本的近端启动子区域，可在体外将上皮特异性表达赋予GFP报告基因。由于这些EGP-2序列可以以EGP-2限制性方式赋予报告基因和自杀基因启动子活性，因此它们可用于表达EGP-2的癌症的基因治疗。