Significant up-regulation of a novel gene, CLCP1, in a highly metastatic lung cancer subline as well as in lung cancers in vivo

Significant up-regulation of a novel gene, CLCP1, in a highly metastatic lung cancer subline as well as in lung cancers in vivo
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DOI:
10.1038/sj.onc.1205405
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发表时间:
2002-04-25
期刊:
影响因子:
8
通讯作者:
Takahashi, T
Takahashi, T
中科院分区:
医学1区
文献类型:
--
作者:
Koshikawa, K;Osada, H;Takahashi, T

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不幸的是,大多数肺癌患者无法治愈,并因广泛转移而死亡,因此表明鉴定在此过程中起关键作用的分子的重要性。我们先前对高转移性肺癌细胞系NCI-H460-LNM 35及其亲本低转移性细胞系NCI-H460-N15的表达谱分析揭示了LNM 35中已知和未知基因的显著上调。在这项研究中,我们描述了一个新的基因,命名为CLCP 1,它对应于这样的表达序列标签与LNM 35中的表达上调之一的分离和详细的表征。发现CLCP 1基因编码具有775个氨基酸的蛋白质,其结构与神经纤毛蛋白、VEGF的细胞表面受体(165)和信号蛋白相似,但不同。值得注意的是,CLCP 1不仅在LNM 35中上调,与其在体内选择过程中获得转移表型相关,而且在体内肺癌的显著部分中上调,在转移性病变中具有高频率,这使得未来的研究能够更好地理解肺癌转移的分子机制。
Most lung cancer patients are unfortunately uncurable and die because of widespread metastases, thus indicating the importance of identification of molecules with a crucial role in this process. Our previous expression profiling analysis of a highly metastatic lung cancer cell line, NCI-H460-LNM35, and its parental low metastatic line, NCI-H460-N15, revealed significant up-regulation of both known and unknown genes in LNM35. In this study, we describe the isolation and detailed characterizations of a novel gene, named CLCP1, which corresponds to one of such expression sequence tags with up-regulated expression in LNM35. The CLCP1 gene was found to encode a protein with 775 amino acids with structural similarities to, but distinct from neuropilins, cell surface receptors for VEGF(165), and semaphorins. Notably, CLCP1 was shown to be upregulated not only in LNM35 in association with its acquisition of metastatic phenotype during in vivo selection, but also in a significant fraction of lung cancers in vivo with high frequency in metastatic lesions, warranting future studies for a better understanding of the molecular mechanisms of lung cancer metastasis.