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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.
- 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.
- Subjects :
- Drug Resistance, Neoplasm genetics
Female
HeLa Cells metabolism
Humans
Male
Neoplasm Proteins metabolism
Prostatic Neoplasms metabolism
Proto-Oncogene Proteins c-bcl-2 metabolism
Transfection
Tumor Cells, Cultured
Antibodies, Monoclonal genetics
Breast Neoplasms metabolism
Neoplasm Proteins immunology
Proto-Oncogene Proteins c-bcl-2 immunology
Subjects
Details
- Language :
- English
- ISSN :
- 0008-5472
- Volume :
- 58
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- Cancer research
- Publication Type :
- Academic Journal
- Accession number :
- 9605757