Up-regulation of PSF2, a member of the GINS multiprotein complex, in intrahepatic cholangiocarcinoma.
Up-regulation of PSF2, a member of the GINS multiprotein complex, in intrahepatic cholangiocarcinoma.
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DOI：
10.3892/or.14.3.701
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发表时间：
2005-09
期刊：
影响因子：
4.2
通讯作者：
K. Obama;Katsuaki Ura;S. Satoh;Yusuke Nakamura;Y. Furukawa
中科院分区：
文献类型：
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作者：
K. Obama;Katsuaki Ura;S. Satoh;Yusuke Nakamura;Y. Furukawa
为了揭示胆管癌发生的分子机制，并寻找新的胆管癌诊断标志物和治疗靶点，我们之前使用cDNA微阵列分析了25例肝内胆管癌（ICCs）的基因表达谱，共包含27,648个基因。在癌细胞中频繁上调的基因中，我们重点关注了PSF2 （SLD 52的伴侣），它是GINS多蛋白复合物的一个组成部分，在DNA复制的起始过程中起着至关重要的作用。临床样本的半定量RT-PCR分析证实PSF2在癌细胞中高水平表达，但在正常重要器官中几乎检测不到该基因的表达。用PSF2特异性短干扰RNA转染ETK-1和HuH28细胞可减少转录量，抑制细胞生长，提示PSF2可能在胆管癌的发生发展中发挥重要作用。本文报道的研究结果为人类胆管癌的发生提供了新的见解，并可能有助于开发新型治疗这种类型肝癌的药物。
To disclose molecular mechanisms of cholangiocarcinogenesis and to search for novel diagnostic markers and therapeutic targets for cholangiocarcinoma, we previously analyzed gene-expression profiles of 25 intrahepatic cholangiocarcinomas (ICCs) by means of a cDNA microarray re-presenting 27,648 genes. Among the genes frequently up-regulated in the cancer cells, we focused on PSF2 (partner of SLD five 2), a component of the GINS multiprotein complex that plays a crucial role in initiation of DNA replication. Semi-quantitative RT-PCR analysis of clinical samples confirmed high levels of PSF2 expression in the cancer cells, but expression of this gene was barely detectable in normal vital organs. Transfection of ETK-1 and HuH28 cells with short-interfering RNA specific to PSF2 reduced the amount of transcript and suppressed cell growth, suggesting that PSF2 may play an important role in development of cholangio-carcinoma. The findings reported here provide new insights into human cholangiocarcinogenesis and may contribute to the development of novel therapeutic drugs for this type of liver cancer.