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Use of the EGP-2/Ep-CAM promoter for targeted expression of heterologous genes in carcinoma derived cell lines

Cancer Gene Therapy volume 11, pages 603–612 (2004)Cite this article

Abstract

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.

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Authors and Affiliations

  1. Department of Pathology and Laboratory Medicine, Section of Medical Biology, University Hospital Groningen, Hanzeplein 1, Groningen, 9713 GZ, The Netherlands

    Pamela MJ McLaughlin, Monika Trzpis, Bart-Jan Kroesen, Wijnand Helfrich, Peter Terpstra, Wim HA Dokter, Marcel HJ Ruiters, Lou FMH de Leij & Martin C Harmsen

  2. GUIDE, Groningen University Institute for Drug Exploration, Oostersingel 59, Groningen, 9713 EZ, The Netherlands

    Pamela MJ McLaughlin, Monika Trzpis, Bart-Jan Kroesen, Wijnand Helfrich, Peter Terpstra, Wim HA Dokter, Marcel HJ Ruiters, Lou FMH de Leij & Martin C Harmsen

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  1. Pamela MJ McLaughlin
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Correspondence to Martin C Harmsen.

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McLaughlin, P., Trzpis, M., Kroesen, BJ. et al. Use of the EGP-2/Ep-CAM promoter for targeted expression of heterologous genes in carcinoma derived cell lines. Cancer Gene Ther 11, 603–612 (2004). https://doi.org/10.1038/sj.cgt.7700725

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