Aberrant methylation of FBN2 in human non-small cell lung cancer
Aberrant methylation of FBN2 in human non-small cell lung cancer
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DOI：
10.1016/j.lungcan.2005.04.013
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发表时间：
2005-10-01
期刊：
影响因子：
5.3
通讯作者：
Kimura, H
中科院分区：
文献类型：
--
作者：
Chen, H;Suzuki, M;Kimura, H
FBN 2是一种大的模块化细胞外基质糖蛋白，已知是人体弹性纤维的关键组分。最近在胰腺癌中发现了由于启动子甲基化导致的FBN 2表达缺失。我们通过逆转录PCR检测了肺癌细胞系中FBN 2的表达，并通过甲基化特异性PCR检测了FBN 2的异常甲基化。FBN 2异常甲基化存在于55%（6/11）的非小细胞肺癌（NSCLC）细胞系中，但在小细胞肺癌细胞系中不存在。在细胞系中，FBN 2的表达缺失和异常甲基化之间的一致性为88%（16个中的14个）。在用去甲基化剂5-氮杂-2 '-脱氧胞苷处理后，在测试的所有六种缺乏FBN 2表达的细胞系中恢复FBN 2表达。在原发性NSCLC中，49%（62/126）的病例存在FBN 2甲基化，而相应的非恶性肺组织中只有7%（5/69）存在FBN 2甲基化，尽管FBN 2甲基化在早期疾病患者中也可检测到，但它常发生在较大肿瘤中（p=0.022）、淋巴结转移（p=0.037）或晚期NSCLC（p=0.014）。肿瘤细胞中FBN 2的甲基化和沉默可能在非小细胞肺癌的发生、侵袭和转移中起重要作用。(c)2005 Elsevier爱尔兰有限公司保留所有权利。
FBN2, a large modular extracellular matrix glycoprotein, is known to be a key component of human elastic fiber. A loss of FBN2 expression due to promoter methylation was recently identified in pancreatic cancer. We examined FBN2 expression by reverse transcription PCR and aberrant methylation of FBN2 by methylation specific PCR in lung cancer cell lines. Aberrant methylation of FBN2 was present in 55% (6 of 11) of non-small cell lung cancer (NSCLC) cell lines, but it absent in small cell lung cancer cell lines. The concordance between loss of expression and aberrant methylation of FBN2 was 88% (14 of 16) in the cell lines. FBN2 expression was restored after treatment with the demethylating agent, 5-aza-2'-deoxycytidine in all six cell lines tested that lacked FBN2 expression. Among primary NSCLC, 49% (62/126) of cases had FBN2 methylation, but only 7% (5/69) of the corresponding nonmalignant lung tissues had it. Although FBN2 methylation was detected even in patients with early stage disease, it occurred frequently in large tumors (p=0.022), with nodal metastasis (p=0.037), or with advanced stages of NSCLC (p=0.014). Methylation and silencing of FBN2 in tumor cells may play an important role in carcinogenesis, invasion, and metastasis of NSCLC. (c) 2005 Elsevier Ireland Ltd. Alt rights reserved.