Epigenetic inactivation of CHFR in nasopharyngeal carcinoma through promoter methylation
Epigenetic inactivation of CHFR in nasopharyngeal carcinoma through promoter methylation
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DOI：
10.1002/mc.20106
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发表时间：
2005-08-01
影响因子：
4.6
通讯作者：
Wang, XH
中科院分区：
文献类型：
--
作者：
Cheung, HW;Ching, YP;Wang, XH
染色体不稳定性（CIN）是人类癌症的细胞遗传学标志。越来越多的证据表明，有丝分裂检查点的损害与CIN的因果关系。CHFR是有丝分裂检查点调节因子之一，其延迟响应于有丝分裂应激的染色体凝聚。CHFR通过启动子CpG超甲基化的表观遗传失活可能导致CIN，并已在几种人类癌症中报道。在这项研究中，我们研究了CHFR基因在鼻咽癌（NPC），前列腺癌，卵巢癌和乳腺癌细胞系中的表达。我们发现CHFR mRNA的表达在所有8个NPC细胞系以及3个人NPC异种移植物中显著降低或检测不到，而非恶性鼻咽细胞系和其他测试的癌细胞系以相对高的水平表达CHFR。CHFR启动子区的甲基化也与NPC细胞系和异种移植物中CHFR表达的降低密切相关。用甲基转移酶抑制剂5-氮杂-2 '-脱氧胞苷处理，导致NPC细胞系中CHFR表达的恢复。更重要的是，CHFR基因启动子区的甲基化在原发性NPC肿瘤中的检出率为61.1%（22/36），而在非恶性组织中则不存在。这些结果表明，CHFR的下调是一个共同的事件，在鼻咽癌细胞，这可能是由于基因启动子区的甲基化。(c)2005 Wiley-Liss，Inc.
Chromosomal instability (CIN) is a cytogenetic hallmark of human cancers. Increasing evidence suggests that impairment of mitotic checkpoint is causally associated with CIN. CHFR is one of the mitotic checkpoint regulators and it delays chromosome condensation in response to mitotic stress. Epigenetic inactivation of CHFR through promoter CpG hypermethylation may lead to CIN and has been reported in several human cancers. In this study, we investigated the CHFR gene expression in a panel of nasopharyngeal carcinoma (NPC), prostate, ovarian, and breast cancer cell lines. We found that the expression of CHFR mRNA was significantly decreased or undetectable in all eight NPC cell lines as well as three human NPC xenografts, whereas non-malignant nasopharyngeal cell lines and other cancer cell lines tested expressed CHFR at relatively high levels. Hype methylation of CHFR promoter region was also strongly correlated with decreased CHFR expression in NPC cell lines and xenografts. Treatment with a methyltransferase inhibitor, 5-aza-2'-deoxycytidine, led to restoration of CHFR expression in NPC cell lines. More importantly, hypermethylation of CHFR promoter region was detected in 61.1% (22 out of 36) of primary NPC tumors while it was absent in non-malignant tissues. These findings suggest that downregulation of CHFR is a common event in NPC cells which may be due to hypermethylation of the gene promoter region. (c) 2005 Wiley-Liss, Inc.