RT Journal Article
SR Electronic
T1 Targeted Gene Expression Using a 1.1 Kilobase Promoter Fragment of the Tumour-associated Antigen EpCAM
JF Anticancer Research
JO Anticancer Res
FD International Institute of Anticancer Research
SP 3715
OP 3722
VO 24
IS 6
A1 OLIVIER GIRES
A1 STEPHANIE PÖCKL
A1 ROB D. CHAPMAN
A1 MARKUS MÜNZ
YR 2004
UL http://ar.iiarjournals.org/content/24/6/3715.abstract
AB The epithelial cell adhesion molecule EpCAM is over- or de novo expressed during carcinogenesis. EpCAM expression correlates with increased proliferation and de-differentiation. Recently, we reported the cloning of a 1.1 kilobase fragment upstream of the epcam gene and demonstrated its specific transcriptional activity. Here, we analyzed the potential of this fragment for targeted gene expression. The fragment was used to regulate the expression of the green fluorescent protein (GFP) and HSV-1 thymidine kinase (HSV-TK), as a model therapeutic gene. Transfection of the pEpProm-control or pEpProm-GFP plasmids resulted in the expression of functional GFP and HSV-TK proteins specifically in EpCAM-positive cells. Expression levels of both proteins correlated with the amount of EpCAM. Additionally, the targeted expression of HSV1-TK transferred a marked sensitivity to ganciclovir treatment in EpCAM-positive HEK293-EBNA1 and SkBr3 carcinoma cells. The EpCAM promoter fragment is, thus, a novel tool to allow for the transcription of therapeutic genes, specifically, in EpCAM-positive carcinomas. Copyright© 2004 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved