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Modulation of Bcl-2 protein levels by an intracellular anti-Bcl-2 single-chain antibody increases drug-induced cytotoxicity in the breast cancer cell line MCF-7.

Authors :
Piché A
Grim J
Rancourt C
Gómez-Navarro J
Reed JC
Curiel DT
Source :
Cancer research [Cancer Res] 1998 May 15; Vol. 58 (10), pp. 2134-40.
Publication Year :
1998

Abstract

Extensive experimental evidence suggests that Bcl-2 promotes cell survival by preventing the onset of apoptosis induced by a variety of stimuli. In addition, Bcl-2 expression has been correlated with resistance and poor response to chemotherapy in a number of cell types. Therefore, this protein represents a logical target for gene therapy strategies designed to achieve selective gene product ablation. In this study, we have developed an approach based upon intracellular expression of single-chain antibodies (sFvs) to achieve modulation of Bcl-2 protein levels in target cells. Using a transient expression system, we show that this intracellular anti-Bcl-2 sFv mediates specific reduction of Bcl-2 levels. This effect significantly enhances drug-mediated cytotoxicity in Bcl-2-overexpressing tumor cells, whereas transfection of the anti-Bcl-2 sFv did not affect the growth rate of the tumor cell lines. This method thus represents a novel and efficient way to selectively abrogate the activity of Bcl-2.

Details

Language :
English
ISSN :
0008-5472
Volume :
58
Issue :
10
Database :
MEDLINE
Journal :
Cancer research
Publication Type :
Academic Journal
Accession number :
9605757