| Apoptotic Pathway Induced by Dominant Negative ATM Gene in CT-26 Colon Cancer Cells |
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Jung Chang Lee1, Ho Keun Yi1, Sun Young Kim1, Dae Yeol Lee1, Pyoung Han Hwang1, Jin Woo Park2 |
1Department of Pediatrics, Schoool of Medicine, Chonbuk National University, Jeonju, Korea
2Department of Biochemistry, Schoool of Medicine, Chonbuk National University, Jeonju, Korea |
| CT-26 대장암 세포에서 Dominant Negative ATM 유전자에 의하여 유도되는 세포자멸사의 경로 |
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이정창1, 이호근1, 김선영1, 이대열1, 황평한1, 박진우2 |
1전북대학교 의과대학 소아과학교실
2전북대학교 의과대학 생화학교실 |
Correspondence:
Pyoung Han Hwang, Email: hwaph@moak.chonbuk.ac.kr
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| 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. |
| Key Words:
Dominant negative ATM, Ionizing radiation, Apoptotic pathway |
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