Journal of Life Science (생명과학회지)

Korean Society of Life Science (한국생명과학회)
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5-Aza-2'-deoxycytidine Inhibits the Maintenance of Cancer Stem Cell in a Mouse Model of Breast Cancer

마우스 유방암 모델에서 5-Aza-2'-deoxycytidine의 암줄기세포 유지 억제 효과

  • Nho, Kyoung-Jin (Center of Animal Care and Use) ;
  • Yang, In-Sook (Center of Animal Care and Use) ;
  • Kim, Ran-Ju (Lab. of Tumor Suppressor, Lee Gil Ya Cancer and Diabetes Institute, Gachon University of Medicine and Science) ;
  • Kim, Soo-Rim (Lab. of Tumor Suppressor, Lee Gil Ya Cancer and Diabetes Institute, Gachon University of Medicine and Science) ;
  • Park, Jeong-Ran (Lab. of Tumor Suppressor, Lee Gil Ya Cancer and Diabetes Institute, Gachon University of Medicine and Science) ;
  • Jung, Ji-Youn (Dept. of Companion and Laboratory Animal Science, Kongju National University) ;
  • Cho, Sung-Dae (Dept. of Oral Pathology, School of Dentistry, Chonbuk National University) ;
  • Nam, Jeong-Seok (Lab. of Tumor Suppressor, Lee Gil Ya Cancer and Diabetes Institute, Gachon University of Medicine and Science)
  • 노경진 (가천의과대학교 이길여 암.당뇨연구원 실험동물센터) ;
  • 양인숙 (가천의과대학교 이길여 암.당뇨연구원 실험동물센터) ;
  • 김란주 (종양억제연구실) ;
  • 김수림 (종양억제연구실) ;
  • 박정란 (종양억제연구실) ;
  • 정지윤 (공주대학교 특수동물학과) ;
  • 조성대 (전북대학교 치과대학 구강병리학과) ;
  • 남정석 (종양억제연구실)
  • Published : 2009.08.30
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Abstract

Aberrant DNA methylation plays an important role in the development of cancer. It has been reported recently that DNA hypermethylation is involved in the maintenance of cancer stem cells. The present study was designed to test the hypothesis that the demethylating agent, 5-aza-2'-deoxycytidine (AZA), can inhibit the potential for maintenance of cancer stem cells. To validate this hypothesis, we used 4T1 syngeneic mouse models of breast cancer. The AZA pre-treated 4T1 cells showed a dramatic inhibition of tumorsphere formation, compared to their counterparts in vitro. In addition, the AZA treatment significantly suppressed the expression of stem regulator genes, such as oct-4, nanog and sox2, compared to counterparts in vivo. Therefore, selective inhibition of DNA methylation may be useful for stem-specific cancer therapy.

비정상적 DNA메칠화는 암 발생에 있어 중요한 역할을 한다. 최근 연구에 의하면 암줄기세포 유지에 있어 DNA과메칠화가 연관되어 있다고 보고하고 있다. 따라서 본 연구는 4T1 유방암 실험모델에서 demethylating agent인 AZA 처리에 따른 후성유전적 변화가 암줄기세포의 유지 및 증식에 있어 어떠한 영향을 미치는지 조사 하였다. 4T1 세포에서 AZA 처리에 따른 tumorsphere 형성이 감소 하는 것을 in vitro 실험을 통해 관찰 하였고, in vivo 실험에서는 줄기세포 조절 유전자들 (Oct-4, Nanog. Sox2)의 발현이 감소 되는 것을 확인 하였다. 본 연구 결과로 볼 때 4T1 유방암 실험모델에서 AZA에 의한 후성유전적 변화는 줄기세포 조절 유전자(SRG)들의 발현을 조절하면서 암줄기세포 특성을 변화시켜 암줄기세포의 증식 및 유지를 억제 할 것으로 사료된다. 향후 이러한 DNA 메칠화 억제를 항암치료에 응용하면, 암줄기세포를 파괴함으로써 암의 재발 및 악성화를 효과적으로 제어 할 수 있을 것으로 사료된다.

Keywords

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