Alteration of Apurinic/Apyrimidinic Endonuclease-1/Redox Factor-1 in Human Mon-small Cell Lung Cancer

비소세포 폐암조직에시 Apurinic/Apyrimidinic Endonuclease-1/Redox Factor-1의 발현변화

  • Yoo, Dae-Goon (Department of Physiology, College of Medicine, Chungnam National University) ;
  • Song, Yun-Jeong (Department of Physiology, College of Medicine, Chungnam National University) ;
  • Cho, Eun-Jung (Department of Physiology, College of Medicine, Chungnam National University) ;
  • Kang, Min-Woong (Department of Thoracic and Cardiovascular Surgery, College of Medicine, Chungnam National University) ;
  • Han, Jong-Hee (Department of Thoracic and Cardiovascular Surgery, College of Medicine, Chungnam National University) ;
  • Na, Myung-Hoon (Department of Thoracic and Cardiovascular Surgery, College of Medicine, Chungnam National University) ;
  • Lim, Seung-Pyung (Department of Thoracic and Cardiovascular Surgery, College of Medicine, Chungnam National University) ;
  • Yu, Jae-Hyeon (Department of Thoracic and Cardiovascular Surgery, College of Medicine, Chungnam National University) ;
  • Jeon, Byeong-Hwa (Department of Physiology, College of Medicine, Chungnam National University) ;
  • Lee, Young (Department of Thoracic and Cardiovascular Surgery, College of Medicine, Chungnam National University)
  • 유대군 (충남대학교 의과대학 생리학교실) ;
  • 송윤정 (충남대학교 의과대학 생리학교실) ;
  • 조은정 (충남대학교 의과대학 생리학교실) ;
  • 강민웅 (충남대학교 의과대학 흉부외과학교실) ;
  • 한종희 (충남대학교 의과대학 흉부외과학교실) ;
  • 나명훈 (충남대학교 의과대학 흉부외과학교실) ;
  • 임승평 (충남대학교 의과대학 흉부외과학교실) ;
  • 유재현 (충남대학교 의과대학 흉부외과학교실) ;
  • 전병화 (충남대학교 의과대학 생리학교실) ;
  • 이영 (충남대학교 의과대학 흉부외과학교실)
  • Published : 2007.08.05

Abstract

Background: An imbalance between oxidants and antioxidants leads to oxidative stress, and this has been proposed to play an important role in the pathogenesis of lung neoplasm. Apurinic/apyrimidinic endonuclease-1/redox factor-1 (APE/ref-1) is a multifunctional protein involved in DNA base excision repair and the redox regulation of many transcription factors. However, the alteration of the expressed levels of APE/ref-1 in non-small cell lung cancer is unknown. Material and Method: Forty-nine patients with surgically resected non-small cell lung cancer (NSCLC) were included in this study. Immunohistochemical staining with APE/ref-1 antibodies was performed, and their expressions were analyzed via Western blotting for specific antibodies. Result: APE/ref-1 was localized at the nucleus and mainly in the non-tumor region of the NSCLC tissue specimens; it was expressed in the cytoplasm and nucleus of the NSCLC. The nuclear and cytoplasmic expressions of APE/ref-1 in lung cancers were markedly up-regulated in the NSCLC, and this was correlated with the clinical stage. Catalase, as first-line antioxidant defense, was dramatically decreased in the NSCLC. Conclusion: Taken together, our results suggest that APE/ref-1, and especially cytoplasmic APE/ref-1, was upregulated in the lung cancer regions, and this may contribute to the compensatory defense system against oxidative stress. A low expression of catalase might have fundamental effects on the extracellular redox state of lung tumors, along with the potential consequences for the tumors.

배경: 산화제와 항산화제 사이의 불균형은 폐암의 발생에 중요한 역할을 하는 것으로 생각되는 산화 스트레스를 유발한다. APE/ref-1은 DNA의 복구와 많은 전사인자들의 산화환원 조절에 연관된 다 기능성 단백질이다. 그러나 폐암에서 APE/ref-1 발현수준의 변화는 알려져 있지 않다. 대상 및 방법: 49명의 수술적으로 제거한 비소세포성 폐암 환자를 대상으로 하였다. APE/ref-1 항체에 대한 면역조직화학적 염색을 하였고, 특이 항체에 대한 Western blot을 시행해 발현 정도를 분석하였다. 결과: APE/ref-1은 주로 폐암 조직의 비 암세포 부분은 핵에 국한되어 존재하였고, 암세포는 핵과 세포질 모두에 존재하였다. 비소세포성 폐암의 핵과 세포질의 APE/ref-1의 발현은 증가되어 있었고 이는 임상적인 병기와도 상관관계를 보였다. 대표적인 항산화 물질인 catalase는 비소세포성 폐암에서 현격하게 감소되어 있었다. 결론: APE/ref-1, 특히 세포질 내의 APE/ref-1의 증가는 산화스트레스에 보상적으로 일어나는 것으로 생각하며 catalase의 감소는 폐암의 특성을 나타내는 세포 외부의 산화환원과정에 근본적인 역할을 하는 것으로 생각한다.

Keywords

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