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Impaired expression of a human septin family gene Bradeion inhibits the growth and tumorigenesis of colorectal cancer in vitro and in vivo

Cancer Gene Therapy volume 9, pages 483–488 (2002)Cite this article

Abstract

We have identified a novel human septin family gene Bradeion, which is specifically expressed in human colorectal cancer and malignant melanoma. In order to analyze the implications of tumor-specific gene expression, ribozymes and its derivatives were specifically designed and transfected into various colorectal adenocarcinoma cell lines for Bradeion inactivation. We constructed ribozyme expression plasmids controlled by a human tRNAVal promoter, and both hammerhead ribozyme and its allosteric derivative maxizyme were used for two different forms of Bradeion mRNA. The sequence-specific cleavage of Bradeion mRNA resulted in significant growth inhibition and G2 arrest in human cancer cell lines, detected by flow cytometry analysis. In addition, in vivo mice studies demonstrated marked tumor growth suppression by the Bradeion-specific ribozymes. Thus, the tumor-specific and selective marker Bradeion also provides valuable tools as a potential target for colorectal cancer therapy.

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Acknowledgements

The authors thank Akira Togiya (Takara Shuzo, Tokyo) for sequence service; Wu-Bo Li (Life Technologies, Rockville, MD), S Hadano and J-E Ikeda (Tokai University), H Kawasaki (Tokyo University), and Y Nagasaka (Beckman Instruments) for valuable discussions and technical advice; and Kenji Sekikawa (National Institute of Agrobiological Sciences) for critical reading of the manuscript.

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  1. Manami Tanaka and Hiroshi Kijima: Manami Tanaka and Hiroshi Kijima contributed equally to this work.

Authors and Affiliations

  1. Department of Collaborations, National Institute of Advanced Industrial Science and Technology, Higashi, Tsukuba Science City, Ibaraki, 305-8566, Japan

    Manami Tanaka, Hiroshi Kijima, Taroh Matsuda & Tomoo Tanaka

  2. Tokai University School of Medicine, Isehara, 259-1193, Kanagawa, Japan

    Hiroshi Kijima, Johbu Itoh & Tomoo Tanaka

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  1. Manami Tanaka
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Correspondence to Manami Tanaka.

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Tanaka, M., Kijima, H., Itoh, J. et al. Impaired expression of a human septin family gene Bradeion inhibits the growth and tumorigenesis of colorectal cancer in vitro and in vivo. Cancer Gene Ther 9, 483–488 (2002). https://doi.org/10.1038/sj.cgt.7700460

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