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

C. Guha, U. Guha, S. Tribius, A. Alfieri, D. Casper, P. Chakravarty, W. Mellado, T. K. Pandita, B. Vikram

Research output: Contribution to journalArticle

35 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)852-858
Number of pages7
JournalGene Therapy
Volume7
Issue number10
DOIs
Publication statusPublished - May 2000

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Keywords

  • ATM
  • Antisense gene therapy
  • Glioblastoma multiforme
  • Radiation therapy

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics

Cite this

Guha, C., Guha, U., Tribius, S., Alfieri, A., Casper, D., Chakravarty, P., ... Vikram, B. (2000). Antisense ATM gene therapy: A strategy to increase the radiosensitivity of human tumors. Gene Therapy, 7(10), 852-858. https://doi.org/10.1038/sj.gt.3301174