Journal of Life Science (생명과학회지)

Korean Society of Life Science (한국생명과학회)
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Resveratrol Up-regulates Cysteine-rich Angiogenic Inducer 61 (CYR61) in Human Colorectal Cancer Cells

Resveratrol에 의한 cysteine-rich angiongenic inducer 61 (CYR61) 유전자의 과대발현 조절

  • Kwak, Eun-Hee (Department of Biological Sciences, Andong National University) ;
  • Kim, Jong-Sik (Department of Biological Sciences, Andong National University)
  • 곽은희 (안동대학교 자연과학대학 생명과학과) ;
  • 김종식 (안동대학교 자연과학대학 생명과학과)
  • Received : 2012.11.19
  • Accepted : 2013.01.25
  • Published : 2013.02.28
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Abstract

In this paper, we investigated whether resveratrol could induce the expression of cysteine-rich angiogenic inducer 61 (CYR61), which is a member of the CCN families. We showed that resveratrol up-regulated CYR61 protein expression in three different human colorectal cancer cell lines. In addition, resveratrol induced CYR61 protein expression in a dose- and time-dependent manner in a HCT116 cell line. To investigate the relationship between various biological activities of resveratrol and CYR61 expression, HCT116 cells were incubated with several NSAIDs, antioxidants, or resveratrol. Interestingly, resveratrol only induced CYR61 protein expression. The expression of CYR61 was not related to the presence of p53. A promoter assay revealed that the 786-bp promoter region (-732/+54) contains a regulatory region and that indole-3-carbinol and 6-gingerol could not induce CYR61 expression. In conclusion, our results indicate up-regulation of CYR61 is extremely resveratrol specific. The results can help to shed light on the unique biological function of resveratrol.

파이토케미칼 resveratrol은 항산화, 항염증, 항암등을 포함하는 다양한 생리활성을 가지고 있는 것으로 알려져 있다. 본 연구에서는 resveratrol이 CCN family 중의 하나인 cysteine-rich angiogenic inducer 61 (CYR61) 유전자의 발현을 유도할 수 있는지 연구하였다. 결과에 의하면 resveratrol은 3개의 다른 인간 대장암 세포주에서 CYR61 단백질의 발현을 유도하였을 뿐만 아니라, HCT116세포주에서는 처리한 resveratrol 농도와 시간 의존적으로 CYR61 단백질의 발현을 유도하였다. 이러한 CYR61 단백질의 발현이 resveratrol의 어떤 생리활성과 관련이 있는지 확인하기 위하여 몇 종류의 NSAIDs와 항산화제를 처리하여 CYR61 단백질의 발현을 확인하였으나, 오직 resveratrol의 처리에 의해서만 CYR61 단백질의 발현이 유도되었다. 또한, CYR61의 발현은 암 억제유전자인 p53과는 관련이 없는 것으로 판단되었다. Promoter assay를 통하여 프로모터 -732 ~ +54 사이에 조절부위가 있음을 확인하였고, 파이토케미칼 Indole-3-carbinol이나 6-gingerol에 의해서도 CYR61의 발현이 유도되지 않음을 확인하였다. 이러한 연구결과는 resveratrol에 의한 CYR61 유전자의 발현은 resveratrol특이적이며, 이러한 연구결과는 resveratrol만의 특이한 생리활성을 이해하는데 도움을 줄 것으로 기대된다.

Keywords

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