J Korean Pediatr Soc.  2003 Jul;46(7):679-686.

Apoptotic Pathway Induced by Dominant Negative ATM Gene in CT-26 Colon Cancer Cells

Affiliations
  • 1Department of Pediatrics, Schoool of Medicine, Chonbuk National University, Jeonju, Korea. hwaph@moak.chonbuk.ac.kr
  • 2Department of Biochemistry, Schoool of Medicine, Chonbuk National University, Jeonju, Korea.

Abstract

PURPOSE
Ataxia telangiectasia mutated(ATM) is involved in DNA damage responses at different cell cycle checkpoints, and signalling pathways associated with regulation of apoptosis in response to ionizing radiation(IR). However, the signaling pathway that underlies IR-induced apoptosis in ATM cells has remained unknown. The purpose of this study was, therefore, to investigate the apoptotic pathway that underlies IR-induced apoptosis in a CT-26 cells expressing dominant negative ATM (DN-ATM).
METHODS
We generated a replication-deficient recombinant adenovirus encoding the DN-ATM(Ad/DN-ATM) or control adenovirus encoding no transgene(Ad/GFP) and infected adenovirus to CT-26 cells. After infection, we examined apoptosis and apoptotic pathway by [3H]-thymidine assay, DNA fragmentation, and Western immunoblot analysis.
RESULTS
DN-ATM gene served as the creation of AT phenotype in a CT-26 cells as revealed by decreased cell proliferations following IR. In addition, IR-induced apoptosis was regulated through the reduced levels of the anti-apoptotic protein Bcl-2, the increased levels of the apoptotic protein Bax, and the activation of caspase-9, caspase-3, and PARP.
CONCLUSION
These results indicate that the pathway of IR-induced apoptosis in CT-26 cells expressing DN-ATM is mediated by mitochondrial signaling pathway involving the activation of caspase 9, caspase 3, and PARP.

Keyword

Dominant negative ATM; Ionizing radiation; Apoptotic pathway
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