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

被引：33
|
作者：
Guha, C
Guha, U
Tribius, S
Alfieri, A
Casper, D
Chakravarty, P
Mellado, W
Pandita, TK
Vikram, B
机构：
[1] Montefiore Med Ctr, Albert Einstein Coll Med, Dept Radiat Oncol, Bronx, NY 10467 USA
[2] Montefiore Med Ctr, Albert Einstein Coll Med, Dept Neurol Surg, Bronx, NY 10467 USA
[3] Beth Israel Med Ctr, New York, NY 10003 USA
[4] Columbia Univ, Ctr Radiol Res, New York, NY 10027 USA
来源：
GENE THERAPY | 2000年 / 7卷 / 10期
关键词：
antisense gene therapy; ATM; radiation therapy; glioblastoma multiforme;
D O I：
10.1038/sj.gt.3301174
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
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.
引用
收藏
页码：852 / 858
页数：7
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