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

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

Research output: Contribution to journalArticle

35 Citations (Scopus)

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
StatePublished - May 2000

Fingerprint

Radiation Tolerance
Genetic Therapy
Ataxia Telangiectasia Mutated Proteins
Antisense RNA
Ataxia Telangiectasia
Glioblastoma
Ionizing Radiation
Genes
DNA Damage
Signal Transduction
Neoplasms
Radiotherapy
DNA
Therapeutics

Keywords

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

ASJC Scopus subject areas

  • 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.

Antisense ATM gene therapy : A strategy to increase the radiosensitivity of human tumors. / Guha, Chandan; Guha, U.; Tribius, S.; Alfieri, A.; Casper, D.; Chakravarty, P.; Mellado, W.; Pandita, T. K.; Vikram, B.

In: Gene Therapy, Vol. 7, No. 10, 05.2000, p. 852-858.

Research output: Contribution to journalArticle

Guha, C, Guha, U, Tribius, S, Alfieri, A, Casper, D, Chakravarty, P, Mellado, W, Pandita, TK & Vikram, B 2000, 'Antisense ATM gene therapy: A strategy to increase the radiosensitivity of human tumors', Gene Therapy, vol. 7, no. 10, pp. 852-858.
Guha C, Guha U, Tribius S, Alfieri A, Casper D, Chakravarty P et al. Antisense ATM gene therapy: A strategy to increase the radiosensitivity of human tumors. Gene Therapy. 2000 May;7(10):852-858.
Guha, Chandan ; Guha, U. ; Tribius, S. ; Alfieri, A. ; Casper, D. ; Chakravarty, P. ; Mellado, W. ; Pandita, T. K. ; Vikram, B. / Antisense ATM gene therapy : A strategy to increase the radiosensitivity of human tumors. In: Gene Therapy. 2000 ; Vol. 7, No. 10. pp. 852-858.
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