Nestin regulates epithelial-mesenchymal transition marker expression in pancreatic ductal adenocarcinoma cell lines
Nestin regulates epithelial-mesenchymal transition marker expression in pancreatic ductal adenocarcinoma cell lines
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DOI：
10.3892/mco.2012.1
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发表时间：
2013-01-01
影响因子：
1.2
通讯作者：
Ishiwata, Toshiyuki
中科院分区：
文献类型：
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作者：
Hagio, Masahito;Matsuda, Yoko;Ishiwata, Toshiyuki
Nestin是一类VI类中间丝，是一种神经干/祖细胞标志物，在包括胰腺导管腺癌（PDAC）在内的各种类型的癌症中也有表达。我们之前在大约30%的PDAC病例中检测到nestin的表达，并发现nestin促进细胞的迁移、侵袭和转移。近年来的研究表明，上皮间充质转化（epithelial mesenchymal transition， EMT）在肿瘤的侵袭和迁移中起重要作用。在本研究中，我们研究了巢蛋白表达的改变是否会影响PDAC细胞中EMT标志物的表达水平。我们使用了两种分别抑制和过表达巢蛋白的PDAC细胞系PK-45H和KLM-1。采用定量RT-PCR分析emt相关分子E-cadherin、Snail、Slug和Twist的表达水平。结果显示，巢蛋白过表达的KLM-1细胞中E-cadherin表达降低，巢蛋白抑制的PK-45H细胞中E-cadherin表达升高。在PDAC细胞中，Snail基因的表达随着巢蛋白的表达而改变，而在巢蛋白过表达的KLM-1细胞中，Slug基因的表达显著降低。Twist基因在两种PDAC细胞系中的表达均低于检测限。本研究结果表明，巢蛋白可能通过调节emt相关分子参与PDAC中癌症行为的控制。
Nestin, a class VI intermediate filament, is a neuronal stem/progenitor cell marker that is also expressed by various types of cancer, including pancreatic ductal adenocarcinoma (PDAC). We previously detected nestin expression in approximately 30% of PDAC cases, and found that nestin promotes the migration, invasion and metastasis of cells. Findings of recent studies have shown that epithelial mesenchymal transition (EMT) is important in the invasion and migration of cancer. In the present study, we investigated whether an altered nestin expression affected the expression levels of EMT markers in PDAC cells. Two human PDAC cell lines, PK-45H and KLM-1, in which nestin was suppressed and overexpressed, respectively, were used. The expression levels of the EMT-related molecules E-cadherin, Snail, Slug and Twist were analyzed using quantitative RT-PCR. Results showed that E-cadherin expression was decreased in nestin-overexpressed KLM-1 cells, and increased in nestin-suppressed PK-45H cells. Snail gene expression in the PDAC cells was altered concomitantly with the changes in nestin expression, while the Slug gene expression was significantly decreased in nestin-overexpressed KLM-1 cells. The Twist gene expression was below the detection limit in the two PDAC cell lines. The present findings indicated that nestin may be involved in the control of cancer behaviors in PDAC via the modulation of EMT-related molecules.