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Science 290 (5493): 989-992

Copyright © 2000 by the American Association for the Advancement of Science

Role of BAX in the Apoptotic Response to Anticancer Agents

Lin Zhang, Jian Yu, Ben Ho Park, Kenneth W. Kinzler, Bert Vogelstein*

To assess the role of BAX in drug-induced apoptosis in human colorectal cancer cells, we generated cells that lack functional BAX genes. Such cells were partially resistant to the apoptotic effects of the chemotherapeutic agent 5-fluorouracil, but apoptosis was not abolished. In contrast, the absence of BAX completely abolished the apoptotic response to the chemopreventive agent sulindac and other nonsteroidal anti-inflammatory drugs (NSAIDs). NSAIDs inhibited the expression of the antiapoptotic protein Bcl-XL, resulting in an altered ratio of BAX to Bcl-XL and subsequent mitochondria-mediated cell death. These results establish an unambiguous role for BAX in apoptotic processes in human epithelial cancers and may have implications for cancer chemoprevention strategies.

Howard Hughes Medical Institute, Oncology Center, and Program in Human Genetics, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
*   To whom correspondence should be addressed. E-mail: vogelbe{at}welch.jhu.edu

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Apaf-1 and caspase-9 do not act as tumor suppressors in myc-induced lymphomagenesis or mouse embryo fibroblast transformation.
C. L. Scott, M. Schuler, V. S. Marsden, A. Egle, M. Pellegrini, D. Nesic, S. Gerondakis, S. L. Nutt, D. R. Green, and A. Strasser (2004)
J. Cell Biol. 164, 89-96
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Sequestration of p53 in the Cytoplasm by Adenovirus Type 12 E1B 55-Kilodalton Oncoprotein Is Required for Inhibition of p53-Mediated Apoptosis.
L. Y. Zhao and D. Liao (2003)
J. Virol. 77, 13171-13181
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Identification of HRK as a Target of Epigenetic Inactivation in Colorectal and Gastric Cancer.
T. Obata, M. Toyota, A. Satoh, Y. Sasaki, K. Ogi, K. Akino, H. Suzuki, M. Murai, T. Kikuchi, H. Mita, et al. (2003)
Clin. Cancer Res. 9, 6410-6418
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Influence of Induced Reactive Oxygen Species in p53-Mediated Cell Fate Decisions.
S. Macip, M. Igarashi, P. Berggren, J. Yu, S. W. Lee, and S. A. Aaronson (2003)
Mol. Cell. Biol. 23, 8576-8585
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