Choi Jin Eun, Kim Dong Sun, Kim Eun Jin, Chae Myung Hwa, Cha Sung Ick, Kim Chang Ho, Jheon Sanghoon, Jung Tae Hoon, Park Jae Yong
Department of Biochemistry, School of Medicine, Kyungpook National University, Dong In 2Ga 101, Daegu, 700-422, South Korea.
Cancer Genet Cytogenet. 2008 Dec;187(2):80-4. doi: 10.1016/j.cancergencyto.2008.08.001.
ADAMTS1 (a disintegrin and metalloproteinase with thrombospondin type 1 motifs) is an extracellular matrix metalloproteinase with protease activity and antiangiogenic activity. It has been suggested that ADAMTS1 plays an important role in tumor growth and metastasis. In this study, we examined ADAMTS1 expression in non-small cell lung cancer (NSCLC), and we also evaluated whether the loss of ADAMTS1 expression is due to aberrant methylation of the gene. In addition, we examined the relationship between ADAMTS1 methylation and clinicopathologic features in NSCLC patients. ADAMTS1 expression was examined using reverse-transcription polymerase chain reaction (PCR), and the methylation status of the gene was evaluated by methylation-specific PCR in NSCLC cell lines (n=10) and primary NSCLC tumors (n=98). Down-regulation of ADAMTS1 was observed in 30% (3/10) of the NSCLC cell lines, and this down-regulation was found to be concordant with aberrant methylation of the gene. Furthermore, ADAMTS1 expression was restored after treatment with the demethylating agent, 5-Aza-2'-deoxycytidine, in cell lines that lacked ADAMTS1 expression. Aberrant methylation of the gene was observed in 31.6% (31 of 98) of the NSCLC tumors, while it was found in only 7.1% (7/98) of the corresponding nonmalignant tissues. Methylation in NSCLC tumors was not correlated with the clinicopathologic features of the patients, such as age, gender, and histology and pathologic staging of the tumor. Taken together, these results suggest that aberrant methylation of ADAMTS1 frequently occurs in NSCLCs and that it may play a role in the pathogenesis of NSCLC.
ADAMTS1（含血小板反应蛋白基序的解聚素样金属蛋白酶1）是一种具有蛋白酶活性和抗血管生成活性的细胞外基质金属蛋白酶。有研究表明，ADAMTS1在肿瘤生长和转移中发挥重要作用。在本研究中，我们检测了非小细胞肺癌（NSCLC）中ADAMTS1的表达情况，还评估了ADAMTS1表达缺失是否归因于该基因的异常甲基化。此外，我们研究了NSCLC患者中ADAMTS1甲基化与临床病理特征之间的关系。采用逆转录聚合酶链反应（PCR）检测ADAMTS1的表达，并通过甲基化特异性PCR评估NSCLC细胞系（n = 10）和原发性NSCLC肿瘤（n = 98）中该基因的甲基化状态。在30%（3/10）的NSCLC细胞系中观察到ADAMTS1表达下调，且这种下调与该基因的异常甲基化一致。此外，在缺乏ADAMTS1表达的细胞系中，用去甲基化剂5-氮杂-2'-脱氧胞苷处理后，ADAMTS1表达得以恢复。在31.6%（98例中的31例）的NSCLC肿瘤中观察到该基因的异常甲基化，而在相应的非恶性组织中仅为7.1%（98例中的7例）。NSCLC肿瘤中的甲基化与患者的临床病理特征，如年龄、性别、肿瘤组织学类型和病理分期均无相关性。综上所述，这些结果表明ADAMTS1的异常甲基化在NSCLC中频繁发生，且可能在NSCLC的发病机制中起作用。
