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韩国非小细胞肺癌中 PTEN 基因的低甲基化。

Infrequent hypermethylation of the PTEN gene in Korean non-small-cell lung cancers.

机构信息

Department of Anatomy, School of Medicine, Kyungpook National University, Daegu, Korea.

出版信息

Cancer Sci. 2010 Feb;101(2):568-72. doi: 10.1111/j.1349-7006.2009.01406.x.

Abstract

CpG islands (CGIs) hypermethylation is implicated in the pathogenesis of many cancers, including lung cancer. The phosphate and tension homolog (PTEN) is a tumor suppressor that controls a variety of biological processes including cell proliferation, growth, migration, and death. The defects in PTEN regulation have a profound impact on carcinogenesis. Herein, we have examined the methylation status of the human PTEN gene in 137 primary non-small-cell lung cancers (NSCLCs) by using a methylation-specific PCR and correlated the results with clinicopathological features. Promoter methylation of the PTEN gene was observed in 5.1%, 2.9%, and 0.0% of three different CpG regions, which were localized at -1460 to -1263, -984 to -848, and -300 to -128 nucleotides upstream of the translation start site, respectively. Reverse transcription-PCR and immunohistochemical analysis showed the methylation of the CGI region at -984 to -848 correlated more accurately with PTEN expression. In addition, no significant correlation was found between PTEN methylation and clinicopathological factors, including the survival rates. These findings suggest that promoter methylation is not an important mechanism for PTEN deregulation in NSCLCs from Koreans.

摘要

CpG 岛(CGIs)的异常甲基化与许多癌症的发病机制有关,包括肺癌。磷酸酶和张力蛋白同源物(PTEN)是一种肿瘤抑制因子,可控制多种生物学过程,包括细胞增殖、生长、迁移和死亡。PTEN 调节的缺陷对致癌作用有深远的影响。在此,我们通过甲基化特异性 PCR 检测了 137 例原发性非小细胞肺癌(NSCLCs)中人类 PTEN 基因的甲基化状态,并将结果与临床病理特征相关联。在三个不同的 CpG 区域中观察到 PTEN 基因的启动子甲基化,分别位于翻译起始位点上游的-1460 至-1263、-984 至-848 和-300 至-128 核苷酸处。逆转录-PCR 和免疫组织化学分析表明,-984 至-848 的 CGI 区域的甲基化与 PTEN 表达更准确相关。此外,PTEN 甲基化与包括生存率在内的临床病理因素之间没有发现显著相关性。这些发现表明,在韩国的 NSCLCs 中,启动子甲基化不是 PTEN 失调控的重要机制。

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