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口腔鳞状细胞癌细胞中热休克蛋白 B1 基因启动子的高甲基化。

Promoter hypermethylation of the gene encoding heat shock protein B1 in oral squamous carcinoma cells.

机构信息

Division of Environmental Health and Occupational Medicine, National Health Research Institutes, Miaoli, Taiwan.

出版信息

Oral Surg Oral Med Oral Pathol Oral Radiol. 2013 Mar;115(3):376-84. doi: 10.1016/j.oooo.2012.12.011.

Abstract

OBJECTIVE

The mechanism responsible for the regulation of HSPB1 expression in oral squamous cell carcinoma was explored in this study.

STUDY DESIGN

The expression and the methylation status of HSPB1 in oral squamous carcinoma cells were examined using real-time reverse transcription-PCR, methylation-specific PCR and pyrosequencing.

RESULTS

HSPB1 expression was weakly expressed in oral squamous carcinoma cell lines (N = 4) as compared to that of normal human oral keratinocytes. The lower expressed HSPB1 was associated with promoter hypermethylation of the HSPB1 gene, and the expression of HSPB1 could be induced by treating the cells with a DNA methyltransferase inhibitor, RG108. Promoter hypermethylation of the HSPB1 gene was also noted in primary oral squamous carcinomas, concomitant with reduced levels of HSPB1 gene expression, as compared to those of the paired neighboring normal tissues.

CONCLUSION

Aberrant promoter hypermethylation of the HSPB1 gene may explain the reduced expression of HSPB1 noted in oral cancer cells.

摘要

目的

本研究旨在探讨口腔鳞状细胞癌中 HSPB1 表达调控的机制。

研究设计

采用实时逆转录-PCR、甲基化特异性 PCR 和焦磷酸测序检测口腔鳞状癌细胞中 HSPB1 的表达和甲基化状态。

结果

与正常人口腔角质细胞相比,HSPB1 在口腔鳞状癌细胞系(N=4)中的表达较弱。表达较低的 HSPB1 与 HSPB1 基因启动子超甲基化有关,用 DNA 甲基转移酶抑制剂 RG108 处理细胞可诱导 HSPB1 的表达。与配对的相邻正常组织相比,HSPB1 基因在原发性口腔鳞状细胞癌中也存在启动子超甲基化,同时 HSPB1 基因的表达水平降低。

结论

HSPB1 基因启动子异常甲基化可能解释了口腔癌细胞中 HSPB1 表达降低的现象。

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