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

PMJ McLaughlin, M Trzpis, BJ Kroesen, W Helfrich, P Terpstra, WHA Dokter, MHJ Ruiters, LF de Leij, MC Harmsen*

*Bijbehorende auteur voor dit werk

OnderzoeksoutputAcademicpeer review

21 Citaten (Scopus)

Samenvatting

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.

Originele taal-2English
Pagina's (van-tot)603-612
Aantal pagina's10
TijdschriftCancer Gene Therapy
Volume11
Nummer van het tijdschrift9
DOI's
StatusPublished - sep-2004

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