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Antisense ATM gene therapy: a strategy to increase the radiosensitivity of human tumors

Gene Therapy volume 7, pages 852–858 (2000)Cite this article

Abstract

Atm, the gene mutated in ataxia-telangiectasia (AT) patients, is an essential component of the signal transduction pathway that responds to DNA damage due to ionizing radiation (IR). We attenuated ATM protein expression in human glioblastoma cells by expressing antisense RNA to a functional domain of the atm gene. While ATM expression decreased, constitutive expression of p53 and p21 increased. Irradiated ATM-attenuated cells failed to induce p53, demonstrated radioresistant DNA synthesis, and increased radiosensitivity. Antisense-ATM gene therapy in conjunction with radiation therapy may provide a novel strategy for the treatment of cancer.

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Acknowledgements

We thank Zoya Niazova and Zuoheng Fan for technical assistance, TK Pandita for providing the pGEM-ATM14 plasmid, J Roy Chowdhury and R Kucheralapati for helpful discussions and reviewing the manuscript. This work was supported by NIH grant (NS 34746 to TKP) and by a pilot project grant from the Department of Radiation Oncology, Montefiore Medical Center, Bronx, NY.

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Authors and Affiliations

  1. Department of Radiation Oncology of the Albert Einstein College of Medicine, Montefiore, New York, NY, USA

    C Guha, U Guha, S Tribius, P Chakravarty & B Vikram

  2. Beth Israel Medical Centers, New York, NY, USA

    A Alfieri

  3. Department of Neurological Surgery of the Albert Einstein College of Medicine, Montefiore, USA

    D Casper

  4. Center for Radiological Research, Columbia University, NY, USA

    W Mellado & T K Pandita

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  1. C Guha
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Guha, C., Guha, U., Tribius, S. et al. Antisense ATM gene therapy: a strategy to increase the radiosensitivity of human tumors. Gene Ther 7, 852–858 (2000). https://doi.org/10.1038/sj.gt.3301174

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