ATM-NF-κB connection as a target for tumor radiosensitization

Kazi Mokim Ahmed, Jian-Jian Li

Research output: Contribution to journalReview article

47 Citations (Scopus)

Abstract

Ionizing radiation (IR) plays a key role in both areas of carcinogenesis and anticancer radiotherapy. The ATM (ataxia-telangiectasia mutated) protein, a sensor to IR and other DNA-damaging agents, activates a wide variety of effectors involved in multiple signaling pathways, cell cycle checkpoints, DNA repair and apoptosis. Accumulated evidence also indicates that the transcription factor NF-κB (nuclear factor-kappaB) plays a critical role in cellular protection against a variety of genotoxic agents including IR, and inhibition of NF-κB leads to radiosensitization in radioresistant cancer cells. NF-κB was found to be defective in cells from patients with A-T (ataxia-telangiectasia) who are highly sensitive to DNA damage induced by IR and UV lights. Cells derived from A-T individuals are hypersensitive to killing by IR. Both ATM and NF-κB deficiencies result in increased sensitivity to DNA double strand breaks. Therefore, identification of the molecular linkage between the kinase ATM and NF-κB signaling in tumor response to therapeutic IR will lead to a better understanding of cellular response to IR, and will promise novel molecular targets for therapy-associated tumor resistance. This review article focuses on recent findings related to the relationship between ATM and NF-κB in response to IR. Also, the association of ATM with the NF-κB subunit p65 in adaptive radiation response, recently observed in our lab, is also discussed.

Original languageEnglish (US)
Pages (from-to)335-342
Number of pages8
JournalCurrent Cancer Drug Targets
Volume7
Issue number4
DOIs
StatePublished - Jun 2007
Externally publishedYes

Fingerprint

Ataxia Telangiectasia
Ionizing Radiation
Neoplasms
Ataxia Telangiectasia Mutated Proteins
Double-Stranded DNA Breaks
Ultraviolet Rays
Cell Cycle Checkpoints
DNA Repair
DNA Damage
Carcinogenesis
Transcription Factors
Phosphotransferases
Radiotherapy
Radiation
Apoptosis
DNA
Therapeutics

Keywords

  • ATM
  • Ionizing radiation
  • NF-κB

ASJC Scopus subject areas

  • Pharmaceutical Science
  • Cancer Research

Cite this

ATM-NF-κB connection as a target for tumor radiosensitization. / Ahmed, Kazi Mokim; Li, Jian-Jian.

In: Current Cancer Drug Targets, Vol. 7, No. 4, 06.2007, p. 335-342.

Research output: Contribution to journalReview article

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