Journal of Life Science (생명과학회지)

Korean Society of Life Science (한국생명과학회)
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A Cancer-specific Promoter for Gene Therapy of Lung Cancer, Protein Regulator of Cytokinesis 1 (PRC1)

폐암의 유전자 치료법을 위한 암특이적인 PRC1 프로모터

  • Cho, Young-Hwa (Juseong Gene Therapy R&D Center, Juseong College) ;
  • Yun, Hye-Jin (Institute for Brain Science and Technology, Inje University) ;
  • Kwon, Hee-Chung (Division of Radiation Cancer, Korea Institute of Radiological and Medical Sciences (KIRAMS)) ;
  • Kim, Hee-Jong (Juseong Gene Therapy R&D Center, Juseong College) ;
  • Cho, Sung-Ha (Juseong Gene Therapy R&D Center, Juseong College) ;
  • Kang, Bong-Su (Juseong Gene Therapy R&D Center, Juseong College) ;
  • Kim, Yeun-Ju (Juseong Gene Therapy R&D Center, Juseong College) ;
  • Seol, Won-Gi (Institute for Brain Science and Technology, Inje University) ;
  • Park, Kee-Rang (Juseong Gene Therapy R&D Center, Juseong College)
  • 조영화 (주성유전자치료기술센터) ;
  • 윤혜진 (인제대학교 뇌과학기술연구소) ;
  • 권희충 (한국원자력의학원) ;
  • 김희종 (주성유전자치료기술센터) ;
  • 조성하 (주성유전자치료기술센터) ;
  • 강봉수 (주성유전자치료기술센터) ;
  • 김연주 (주성유전자치료기술센터) ;
  • 설원기 (인제대학교 뇌과학기술연구소) ;
  • 박기랑 (주성유전자치료기술센터)
  • Published : 2008.10.30
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Abstract

We have recently reported the PRC1 promoter as a promoter candidate to control expression of transcriptionally targeted genes for breast cancer gene therapy. We tested whether the PRC1 promoter could be also applied for the lung cancer gene therapy. In the transient transfection assay with naked plasmids containing the luciferase fused to the PRC1 promoter, the promoter showed little activity in the normal lung cell line, MRC5. However, in the lung cancer A549 cells, PRC1 showed approximately 30-fold activation which was similar to the survivin promoter, the gene whose promoter has been already reportedas a candidate for the gene therapy of lung cancer. In viral systems, the PRC1 promoter showed approximately 75% and 66% of transcriptional activity compared to the CMV promoter in the adeno-associated virus (AAV) and the adenovirus (AV) systems, respectively. However, the PRC1 promoter in either AAV or AV showed approximately 20% activity compared to the CMV promoter in the normal lung cells. In addition, human lung tumor xenograft mice showed that the PRC1 promoter activity was as strong as the CMV activity in vivo. Taken together, these results suggested that PRC1 might be a potential promoter candidate for transcriptionally targeted lung cancer gene therapy.

우리는 최근에 PRC1 프로모터가 유방암 유전자치료를 위하여 전사 표적이 된 유전자의 발현을 조절할 수 있는 후보 프로모터임을 보고하였다. 우리는 본 실험에서 PRC1이 폐암유전자 치료에서도 적용이 가능한지 조사하였다. 특정 프로모터가 루시퍼라제 유전자와 연결된 플라스미드를 이용한 형질전환 assay에서 PRC1 프로모터는 정상폐세포주에서는 활성을 보이지 않으나 폐암세포주에선 약 30 배의 활성을 보였다. 이는 이미 암특이적인 발현으로 알려진 BIRC5 (survivin) 프로모터와 유사한 결과였다. 또한, 바이러스 벡터를 이용한 실험에서 PRC1은 CMV 프로모터에 비해 아데노부속바이러스에서 약 75%, 아데노바이러스에서 약 66%의활성을 보였다. 이와 대조적으로, PRC1 프로모터를 함유한 이 들 두 종류의 바이러스는 정상 폐세포에서는 20%정도의 낮은 활성을 보였다. 흥미롭게도, 인간 폐종양세포를 이식한 생쥐모델을 사용한 결과에서는 PRC1 프로모터가 CMV 프로모터와 비슷한 생체 활성을 보였다. 종합하면, 이상의 결과는 PRC1이 폐암 유전자치료를 위한 전사표적 유전자의 발현을 위한 프로모터로 사용 가능함을 암시한다.

Keywords

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