Aberrant promoter hypermethylation of the CHFR gene in oral squamous cell carcinomas
Aberrant promoter hypermethylation of the CHFR gene in oral squamous cell carcinomas
复制标题
DOI：
10.3892/or_00000552
复制
发表时间：
2009-11-01
期刊：
影响因子：
4.2
通讯作者：
Shibata, Toshiyuki
中科院分区：
文献类型：
--
作者：
Baba, Seiji;Hara, Akira;Shibata, Toshiyuki
近年来的研究表明，抑癌基因启动子区甲基化是多种人体器官癌变的重要因素。本研究的目的是检测一种新的细胞周期调控基因CHFR在原发性口腔癌肿瘤和癌旁正常粘膜中的甲基化状态，并阐明甲基化状态与CHFR相关的染色体乘客蛋白Aurora-A表达之间的关系。应用甲基化特异性PCR（MSP）方法检测49例口腔鳞状细胞癌（OSCC）和6株OSCC细胞系CHFR基因甲基化状态。13例同时检查了邻近正常口腔粘膜组织。18例健康志愿者的正常口腔粘膜作为对照。采用实时荧光定量RT-PCR方法检测口腔鳞癌细胞系中Aurora-A和CHFR的mRNA水平，并采用免疫组化方法检测Aurora-A蛋白的表达。CHFR基因启动子区异常甲基化发生率为34.7%（17/49）。在13例癌组织和癌旁正常组织中，CHFR基因启动子区甲基化率为46.1%（6/13）。相比之下，CHFR基因的启动子甲基化仅在7.7%（1/13）的周围正常粘膜中被识别。在健康志愿者中未检测到CHFR基因的超甲基化。只有一个OSCC细胞系显示CHFR基因的高甲基化，同时沉默mRNA表达，然而，Aurora-A在所有细胞系中大量表达。此外，CHFR基因甲基化状态与Aurora-A蛋白在口腔鳞癌中的表达无明显关系。CHFR基因甲基化在口腔鳞状细胞癌组织中存在，而在癌旁正常口腔组织中的发生率很低。虽然需要进一步的研究，Aurora-A基因的表达似乎是独立的甲基化状态的CHFR基因在口腔鳞癌。
Recent studies have shown that promoter hypermethylation of tumor suppressor genes is an important factor in carcinogenesis of several human organs. The purpose of this study was to examine the methylation status of CHFR, a novel cell cycle regulatory gene, in both primary oral cancer tumors and the adjacent normal mucosa, and to clarify the relation between the methylation status and expression of the CHFR-related chromosomal passenger protein Aurora-A. The methylation status of the CHFR gene was examined by the methylation-specific PCR (MSP) in 49 primary oral squamous cell carcinomas (OSCC) and 6 OSCC cell lines. In 13 cases, the adjacent normal oral mucosal tissues were also examined. Normal oral mucosa from 18 healthy volunteers was used as the control. The mRNA level of Aurora-A and CHFR in OSCC cell lines was investigated by real-time RT PCR and the protein expression of Aurora-A in certain tumor samples was confirmed by immunohistochemistry. Aberrant promoter methylation of the CHFR gene was detected in 34.7% (17 of 49) of OSCC cases. As for the 13 OSCC cases with paired cancerous and adjacent normal tissues, promoter hypermethylation of the CHFR gene was detected in 46.1% (6 of 13) of the cancerous tissues. In contrast, promoter hypermethylation of the CHFR gene was recognized in only 7.7% (1 of 13) of the surrounding normal mucosa. No hypermethylation of the CHFR gene was detected in healthy volunteers. Only one OSCC cell line shows hypermethylation of the CHFR gene with concurrently silenced mRNA expression, however, Aurora-A was expressed abundantly in all cell lines. Furthermore, there is no significant relationship between methylation status of the CHFR gene and Aurora-A protein expression in OSCC. Hypermethylation of the CHFR gene was detected in a certain part of OSCC cases whereas it had very low frequency in adjacent normal oral tissues. Although further study is needed, Aurora-A gene expression seems to be independent from methylation status of the CHFR gene in OSCC.