Radiation Oncology Journal

  • 제22권3호
  • /
  • Pages.208-216
  • /
  • 2004
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  • 2234-1900(pISSN)
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  • 2234-3156(eISSN)
대한방사선종양학회 (The Korean Society for Radiation Oncology)
권호 표지

두경부종양 세포주에서 Ku 단백질 발현 정도에 따른 방사선 민감도

Expression of Ku Correlates with Radiation Sensitivities in the Head and Neck Cancer Cell Lines

  • 이상욱 (울산대학교 의과대학 서울아산병원 방사선종양학과) ;
  • 유은실 (울산대학교 의과대학 서울아산병원 병리과) ;
  • 이소령 (울산대학교 의과대학 서울아산병원 방사선종양학과) ;
  • 손세희 (울산대학교 의과대학 서울아산병원 방사선종양학과) ;
  • 김종훈 (울산대학교 의과대학 서울아산병원 방사선종양학과) ;
  • 안승도 (울산대학교 의과대학 서울아산병원 방사선종양학과) ;
  • 신성수 (울산대학교 의과대학 서울아산병원 방사선종양학과) ;
  • 최은경 (울산대학교 의과대학 서울아산병원 방사선종양학과)
  • Lee Sang-wook (Departments of Radiation Oncology, University of Ulsan College of Medicine, Asan Medical Center, Seoul) ;
  • Yu Eunsil (Departments of Pathology, University of Ulsan College of Medicine, Asan Medical Center, Seoul) ;
  • Yi So-Lyoung (Departments of Radiation Oncology, University of Ulsan College of Medicine, Asan Medical Center, Seoul) ;
  • Son Se-Hee (Departments of Radiation Oncology, University of Ulsan College of Medicine, Asan Medical Center, Seoul) ;
  • Kim ong Hoon (Departments of Radiation Oncology, University of Ulsan College of Medicine, Asan Medical Center, Seoul) ;
  • Ahn Seung Do (Departments of Radiation Oncology, University of Ulsan College of Medicine, Asan Medical Center, Seoul) ;
  • Shin Seong Soo (Departments of Radiation Oncology, University of Ulsan College of Medicine, Asan Medical Center, Seoul) ;
  • Choi Eun Kyung (Departments of Radiation Oncology, University of Ulsan College of Medicine, Asan Medical Center, Seoul)
  • 발행 : 2004.09.01
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초록

목적: DNA-dependent protein kinase (DNA-PK)는 serine/threonine kinase로 470 kDa의 catalytic subunit (DNA- PKcs) 와 각각 70 kDa과 86 kDa의 무게를 갖는 Ku 70, Ku 80 단백질로 구성된다. 이 DNA-PK는 방사선에 의해 DNA의 두 가닥이 동시에 절단되는 경우 DNA 손상 복구에 핵심적 역할을 하는 것으로 알려져 있다. 본 연구에서 Ku 발현과 이온화방사선에 민감도와의 상관 관계를 알아보고자 하였다. 대상 및 방법: 예비실험으로 두경두종양 기원의 세포주 9개에 대한 방사선에 대한 민감도실험을 한 결과 AMC-HN3이 방사선에 가장 민감하였고, AMC-HN9이 방사선에 가장 저항성을 보여 2개의 세포주에 대한 Ku70/80의 발현을 Western blot과 면역형광 염색을 시행하여 방사선의 반응도와의 상관관계를 알아보았다. 결과: 방사선에 저항성을 보이는 AMC-HN9에서 Ku80 발현이 높았고 방사선에 민감한 AMC-HN3에서 세포자멸사가 더 많이 일어남을 관찰할 수 있었다. 결론: Ku80 단백질 발현이 높은 세포는 방사선에 대한 DNA손상 복구가 많이 되어 방사선에 대한 내성을 보이는 것으로 생각되었다.

Purpose: DNA-dependent protein kinase (DNA-PK) is a serine/threonine kinase consisting of a 470 kDa catalytic subunit (DNA-PKcs) and a heterodimeric regulatory complex, called Ku, which is composed of 70 kDa(Ku 70) and 86 kDa (Ku 80) proteins. The DNA-PK has been shown to play a pivotal role in rejoining DNA double-strand-breaks (dsb) in mammalian cells. The purpose of this study is to examine the relationship between the level of Ku expression and radiation sensitivity. Methods and Materials: Nine head and neck, cancer cell lines showed various intrinsic radiation sensitivities. Among the nine, AMC-HN-3 cell was the most sensitive for X-ray irradiation and AMC-HN-9 cell was the most resistance. The most sensitive and resistant cell lines were selected and the test sensitivity of radiation and expression of Ku were measured. Radiation sensitivity was obtained by colony forming assay and Ku protein expression using Western blot analysis. Results: Ku80 increased expression by radiation, wheres Ku70 did not. Overexpression of Ku80 protein increased radiation resistance in AMC-HN9 cell line. There was a correlation between Ku8O expression and radiation resistance. Ku80 was shown to play an important role in radiation damage response. Conclusion: Induction of Ku80 expression had an important role in DNA damage repair by radiation. Ku80 expression may be an effective predictive assay of radiosensitivity on head and neck cancer.

키워드

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