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Overexpression of the death-promoting gene bax-alpha which is downregulated in breast cancer restores sensitivity to different apoptotic stimuli and reduces tumor growth in SCID mice

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Item Type:Article
Title:Overexpression of the death-promoting gene bax-alpha which is downregulated in breast cancer restores sensitivity to different apoptotic stimuli and reduces tumor growth in SCID mice
Creators Name:Bargou, R.C. and Wagener, C. and Bommert, K. and Mapara, M.Y. and Daniel, P.T. and Arnold, W. and Dietel, M. and Guski, H. and Feller, A. and Royer, H.D. and Doerken, B.
Abstract:We have studied the expression of members of the bcl-2 family in human breast cancer. The expression pattern of these genes in breast cancer tissue samples was compared with the expression pattern in normal breast epithelium. No marked difference with regard to bcl-2 and bcl-xL expression was observed between normal breast epithelium and cancer tissue. In contrast, bax-alpha, a splice variant of bax, which promotes apoptosis, is expressed in high amounts in normal breast epithelium, whereas only weak or no expression could be detected in 39 out of 40 cancer tissue samples examined so far. Of interest, downregulation of bax-alpha was found in different histological subtypes. Furthermore, we transfected bax-alpha into breast cancer cell lines under the control of a tetracycline-dependent expression system. We were able to demonstrate for the first time that induction of bax expression in breast cancer cell lines restores sensitivity towards both serum starvation and APO-I/Fas-triggered apoptosis and significantly reduces tumor growth in SCID mice. Therefore, we propose that dysregulation of apoptosis might contribute to the pathogenesis of breast cancer at least in part due to an imbalance between members of the bcl-2 gene family.
Keywords:Apoptosis, Base Sequence, bcl-2-Associated X Protein, Breast, Breast Neoplasms, CD95 Antigens, Cell Division, Cell Line, Cultured Tumor Cells, DNA Primers, Epithelium, Genetic Transcription, Messenger RNA, Molecular Sequence Data, Neoplasm DNA, Neoplastic Gene Expression Regulation, Polymerase Chain Reaction, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-bcl-2, Recombinant Proteins, Reference Values, Transfection, Animals, Mice
Source:Journal of Clinical Investigation
ISSN:0021-9738
Publisher:American Society for Clinical Investigation (U.S.A.)
Volume:97
Number:11
Page Range:2651-2659
Date:1 June 1996
Official Publication:https://doi.org/10.1172/JCI118715
PubMed:View item in PubMed

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