| A Roles of Apoptotic Genes in Colon Cancers |
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Jae Young Jang, Hyo Jong Kim, Sung-Gil Chi, Kil Yeon Lee, Ki Deuk Nam, Nam Hoon Kim, Sang Kil Lee, Kwang Ro Joo, Seok Ho Dong, Byung-Ho Kim, Young Woon Chang, Joung Il Lee, Rin Chang |
1Department of Internal Medicine, Pathology
2and Surgery, Kyung Hee University College of Medicine, Seoul, Korea
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| 대장암에서 세포자멸사 관련 유전자의 역할 |
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장재영, 김효종, 지성길, 이길연, 남기덕, 김남훈, 이상길, 주광로, 동석호, 김병호, 장영운, 이정일, 장린 |
1경희대학교 의과대학 내과학교실, 병리학교실
2외과학교실 |
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| Abstract |
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Badkground/Aims: X-linked inhibitor of apoptosis (XIAP) is the most potent member of the IAP family that exerts antiapoptotic effects. Recently, XIAP-associated factor 1 (XAF1) and two mitochondrial proteins, Smac/DIABLO and HtrA2, have been identified to negatively regulate the caspase-inhibiting activity of XIAP. We explored the candidacy of XAF1, Smac/DIABLO and HtrA2 as a tumor suppressor in colonic carcinogenesis. Methods: The expression and mutation status of the genes were assessed in 10 colorectal carcinoma cell lines. Results: XAF1 transcript was not expressed or present at extremely low levels in 60% (6/10) of cancer cell lines whereas Smac/DIABLO and HtrA2 are normally expressed in all cell lines examined. XAF1 transcript was reactivated in all low expressor cell lines by treatment with the demethylating agent 5-aza-2'-deoxycytidine. Moreover, bisulfite DNA sequencing analysis for 34 CpG sites in the promoter region revealed a strong association between hypermethylation and gene silencing. Restoration of XAF1 expression resulted in enhanced apoptotic response to etoposide and 5-flurouracil. Conclusions: XAF1 undergoes epigenetic gene silencing in a considerable proportion of human colon cancers by aberrant promoter hypermethylation, suggesting that XAF1 inactivation might be implicated in colonic tumorigenesis. (Intestinal Research 2004;2:71-76) |
| Key Words:
XAF1, Gene, Tumor suppressor, Colonic neoplasms, Apoptosis |
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