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Gires, O. ; Pöckl, S.* ; Chapman, R.D. ; Münz, M.

Targeted gene expression using a 1.1 kilobase promoter fragment of the tumour-associated antigen EpCAM.

Anticancer Res. 24, 3715-3721 (2004)
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The epithelial cell adhesion molecule EpCAM is over- or de novo expressed during carcinogenesis. EpCAM expression correlates with increased proliferation and dedifferentiation. 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.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter EpCAM; promoter; targeted gene expression; HSV1-TK; GFP; CELL ADHESION MOLECULE; OVARIAN-CARCINOMA; EP-CAM; PROLIFERATION; ANTIBODY
ISSN (print) / ISBN 0250-7005
e-ISSN 1791-7530
Zeitschrift Anticancer Research
Quellenangaben Band: 24, Heft: 6, Seiten: 3715-3721 Artikelnummer: , Supplement: ,
Verlag International Institute of Anticancer Research
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Research Unit Gene Vector (AGV)