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  • Original Paper
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Relative level of expression of Bax and Bcl-XL determines the cellular fate of apoptosis/necrosis induced by the overexpression of Bax

Oncogene volume 18, pages 5703–5713 (1999)Cite this article

Abstract

The Bax protein plays a critical role in the apoptosis of cancers induced by radiotherapy or chemotherapy, which induce both apoptosis and necrosis. We transduced various glioblastoma cells with the Bax gene via an adenoviral vector and found that A-172 cells led to necrotic cell death, while U251 cells apoptotic cell death, even though a similar level of Bax protein was introduced. A-172 cells displayed a much higher constitutive expression of the Bcl-XL protein compared with that of U251 cells. Upon simultaneous overexpression of the Bcl-XL and Bax proteins in the U251 cells, Bax-induced apoptosis of U251 cells was suppressed and an increase in the number of necrotic cells was seen. Moreover, induction of a higher amount of Bax protein in A-172 cells increased the percentage of apoptotic cells. In conclusion, if a cancerous cell expresses a high enough amount of Bax to undergo death, apoptosis will be induced. If a cancerous cell expresses a level of Bcl-XL which prevents Bax-induced apoptosis, the overexpression of Bax leads to necrotic cell death.

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Acknowledgements

We thank Dr S Fukuda for assistance with the electron microscopic studies, Dr I Saito for providing the pAxCALNL cosmid construct and the AxCANCre virus, and Dr H Shinoura and R Sato for technical assistance. This work was supported in part by a special grant for Advanced Research on Cancer from the Ministry of Education, Culture and Science of Japan, and grants from the Ministry of Health and Welfare of Japan.

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Authors and Affiliations

  1. Department of Molecular Biotherapy Research, Cancer Chemotherapy Center, 1-37-1 Kami-Ikebukuro, Toshima-ku, 170-8455, Tokyo, Japan

    Nobusada Shinoura, Yoko Yoshida & Hirofumi Hamada

  2. Department of Neurosurgery, Tokyo University, 7-3-1 Hongo, Bunkyo-ku, 113, Tokyo, Japan

    Nobusada Shinoura, Akio Asai & Takaaki Kirino

  3. CREST (Core Research for Evolutional Science and Technology), Japan

    Takaaki Kirino

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  1. Nobusada Shinoura
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Shinoura, N., Yoshida, Y., Asai, A. et al. Relative level of expression of Bax and Bcl-XL determines the cellular fate of apoptosis/necrosis induced by the overexpression of Bax. Oncogene 18, 5703–5713 (1999). https://doi.org/10.1038/sj.onc.1202966

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