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EGR2 induces apoptosis in various cancer cell lines by direct transactivation of BNIP3L and BAK

Oncogene volume 22, pages 2172–2185 (2003)Cite this article

Abstract

EGR2 plays a key role in the PTEN-induced apoptotic pathway. Using adenovirus-mediated gene transfer to 39 cancer cell lines, we found that EGR2 could induce apoptosis in a large proportion of these lines by altering the permeability of mitochondrial membranes, releasing cytochrome c and activating caspase-3, -8, and -9. Analysis by cDNA microarray and subsequent functional studies revealed that EGR2 directly transactivates expression of BNIP3L and BAK. Our results helped to clarify the molecular mechanism of the apoptotic pathway induced by PTEN-EGR2, and suggested that EGR2 may be an excellent target molecule for gene therapy to treat a variety of cancers.

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Acknowledgements

We thank Hiroyuki Kuramoto (Kitasato University, Sagamihara, Japan), Masato Nishida (Kasumigaura National Hospital, Tsuchiura, Japan), Toyomi Satoh (University of Tsukuba, Tsukuba, Japan), and Isamu Ishiwata (Ishiwata Obstetrics and Gynecologie Hospital, Mito, Japan) for their help in obtaining endometrial cancer cell lines, and Yoichi Furukawa (The University of Tokyo, Tokyo, Japan), Takashi Shimokawa (The University of Tokyo) and Yumi Nakajima (Oncotherapy, Tokyo, Japan) for their helpful advice and discussion. This work was supported in part by Research for the Future Program Grant #00L01402 from the Japan Society for the Promotion of Science (JSPS), and the Research Fellowship of JSPS for Young Scientists.

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  1. Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo, 4-6-1 Shiorokanedai, Minato-ku, Tokyo, 108-8639, Japan

    Motoko Unoki & Yusuke Nakamura

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  1. Motoko Unoki
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Correspondence to Yusuke Nakamura.

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Unoki, M., Nakamura, Y. EGR2 induces apoptosis in various cancer cell lines by direct transactivation of BNIP3L and BAK. Oncogene 22, 2172–2185 (2003). https://doi.org/10.1038/sj.onc.1206222

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