Journal of Chest Surgery

The Korean Society for Thoracic and Cardiovascular Surgery (대한심장혈관흉부외과학회)
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Identification of Tumor Suppressor Genes on Chromosome 21

제21번 염색체의 종양억제유전자 발굴

  • Lee, Eung-Bae (Department of Thoracic and Cardiovascular Surgery, Kyungpook National University Hospital, College of Medicine, Kyungpook National University) ;
  • Choi, Jin-Eun (Department of Biochemistry, School of Medicine, Kyungpook National University) ;
  • Jang, Jin-Sung (Department of Biochemistry, School of Medicine, Kyungpook National University) ;
  • Park, Jae-Yong (Department of Internal Medicine, Kyungpook National University Hospital, College of Medicine, Kyungpook National University)
  • 이응배 (경북대학교 의과대학 경북대학교병원 흉부외과학교실) ;
  • 최진은 (경북대학교 의학전문대학원 생화학교실) ;
  • 장진성 (경북대학교 의학전문대학원 생화학교실) ;
  • 박재용 (경북대학교 의과대학 경북대학교병원 내과학교실)
  • Published : 2009.04.05
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Abstract

Background: We performed this study to identify the tumor suppressor genes located in the long arm of chromosome 21 in non-small cell lung cancer. Material and Method: The genes of USP25 in 21q11.2, NCAM2, ADAMTS1 in 21q21.2, and Claudin-8 (CLDN8), Claudin-17 (CLDN17) and TIAM1 in 21q22.1 were investigated for their gene expressions, genetic alterations and promoter methylation. Result: The expressions of CLDN8 and CLDN17 were significantly decreased in 7 (L132, H157, H358, H522, H1299, H1703 and HCC2108) of 13 cell lines, and the expression of ADAMTS1 was also significantly reduced in 6 cell lines (A549, SW900, H1299, H1373, H1703 and H1793). There were no genetic alterations by PCR-SSCP and cDNA cloning in the cell lines with a decreased gene. In the cell lines with a decreased gene expression, the mRNA expression was increased significantly with treatment of 5-Aza-CdR. Conclusion: These results suggest that the ADMTS1, CLDN8 and CLDN17 may act as tumor suppressor genes.

배경: 폐암의 암화과정에 관여하는 21번 염색체 장완에 존재하는 종양억제유전자를 발굴하고자 하였다. 대상 및 방법: 21q11.2 구역의 USP25, 21q21.2 구역의 NCAM2, ADAMTS1, 그리고 21q22.1 구역의 Claudin-8 (CLDN8), Claudin-17 (CLDN17), TIAM1 유전자를 대상으로 비소세포폐암 세포주에서 이들 유전자의 발현 정도와 돌연변이 및 촉진자 메틸화 유무를 조사하였다. 결과: 13가지 비소세포폐암 세포주 가운데 7가지 세포주(L132, H157, H358, H522, H1299, H1703, HCC2108)에서 CLDN8, CLDN17의 발현이 유의하게 감소되었고, ADAMTS1의 경우 6가지 세포주(A549, SW900, H1299, H1373, H1703, H1793)에서 발현양이 유의하게 감소되었다. 유전자 발현의 감소가 있는 세포주와 그렇지 않은 세포주간의 PCR-SSCP의 band pattern의 차이가 없으며 염기서열의 분석에서도 genetic alteration은 관찰되지 않았다. 발현이 감소되어 있는 세포주에 5-Aza-CdR을 처리한 경우 유전자의 발현양이 유의하게 증가되었다. 결론: ADMTS1, CLDN8, CLDN17 유전자는 폐암의 암화과정에 관여하는 종양억제유전자일 가능성을 시사하며, 유전자의 발현 감소는 유전자 촉진자 부위의 methylation에 의함을 시사한다.

Keywords

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