Journal of Life Science (생명과학회지)

Korean Society of Life Science (한국생명과학회)
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Induction of G2/M Cell Cycle Arrest by Glutamine Deprivation in Human Prostate Carcinoma PC3 Cells

글루타민 결핍에 의한 PC3 인체 전립선 암세포의 G2/M 세포주기 억제 유발

  • Shin, Dong Yeok (Dongnam Institute of Radiological & Medicine Sciences) ;
  • Choi, Sung Hyun (Department of System Management, Korea Lift College) ;
  • Park, Dong Il (Department of Internal Medicine, Dongeui University College of Oriental Medicine) ;
  • Choi, Yung Hyun (Department of Biochemistry, Dongeui University College of Oriental Medicine)
  • 신동역 (동남권원자력의과학원) ;
  • 최성현 (한국승강기대학교 승강기시스템관리과) ;
  • 박동일 (동의대학교 한의과대학 내과학교실) ;
  • 최영현 (동의대학교 한의과대학 생화학교실)
  • Received : 2013.04.28
  • Accepted : 2013.06.26
  • Published : 2013.06.30
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Abstract

In this study, it was investigated the possible mechanisms by which glutamine deprivation exerts its anti-proliferative action in cultured human prostate carcinoma PC3 cells. Glutamine deprivation resulted in inhibition of growth and G2/M arrest of the cell cycle in a time-dependent manner without apoptosis induction, as determined by MTT assay, DAPI staining and flow cytometry analyses. The induction of G2/M arrest by glutamine deprivation was associated with the inhibition of expression of Cdc2, cyclin A and cyclin B1, and up-regulation of the expression of cyclin-dependent kinase (Cdk) inhibitor p21(WAF1/CIP1) in both transcriptional and translational levels. Moreover, glutamine deprivation increased the phosphorylation of checkpoint kinase (Chk)1 and Chk2; however, the levels of Cdc25C phosphorylation were decreased in response to glutamine deprivation in a time-dependent manner. Our data provide a first biochemical evidence that glutamine deprivation suppresses cell viability through G2/M phase arrest without induction of apoptosis in PC3 cells.

본 연구에서는 생체 내 구성요소 및 에너지원으로서 중요한 역할을 하는 글루타민 결핍에 의한 인체 전립선 PC3 암세포의 증식에 관한 기전 연구를 실시하였다. 글루타민 결핍에 의한 PC3 세포의 증식억제는 세포주기 G2/M arrest와 연관성이 있었으나, apoptosis 유발 현상은 관찰되지 않았다. 글루타민 결핍에 의한 G2/M arrest는 전사 및 번역 수준에서 Cdc2, cyclin A 및 cyclin B1의 발현 억제 및 p53 비의존적인 p21(WAF1/CIP1)의 발현 증가와 연관성이 있었다. 아울러 글루타민 결핍은 Chk1 및 Chk2의 인산화를 증가시켰으나, Cdc25C의 인산화는 감소시켰다. 본 연구의 결과는 글루타민 결핍에 의한 PC3 세포의 증식억제가 apoptosis 유발과는 상관없이 G2/M arrest를 유발시킨다는 첫 번째 증거이다.

Keywords

References

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