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胰腺癌侵袭转移分析:紧密连接蛋白2的表达与排列和胰腺癌细胞解离之间的相关性

Analysis of invasion-metastasis in pancreatic cancer: Correlation between the expression and arrangement of tight junction protein-2 and cell dissociation in pancreatic cancer cells.

作者信息

Zhou Lei, Tan Xiaodong, Wang Wei, Wang Baosheng, Dai Xianwei, Liu Jingang

机构信息

Department of Hepato-pancreato-biliary Tumor Surgery, China Medical University Shengjing Hospital, Shenyang 110004, P.R. China.

出版信息

Mol Med Rep. 2010 Jan-Feb;3(1):149-53. doi: 10.3892/mmr_00000232.

Abstract

High frequency of invasion and metastasis is one of the key characteristics of pancreatic cancer. In our recent study, tight junction protein-2 (Tjp-2) was identified as a differentially expressed gene related to invasion-metastasis in highly (PC-1.0) and weakly (PC-1) invasive and metastatic pancreatic cancer cells by cDNA microarray analysis. Changes in the structure and function of tight junctions are correlated with carcinogenesis and tumour development. In this study, RT-PCR, Western blotting and immunocytochemistry were used to study the correlation between the expression and localisation of Tjp-2 and cell dissociation in pancreatic cancer. Tjp-2 mRNA and protein were differentially expressed in PC-1.0 and PC-1 cells. Furthermore, the addition of dissociation factor (DF) or U0126 (a MEK inhibitor) significantly induced changes in the mRNA expression and protein intracellular localisation of Tjp-2, and in the simultaneous cell dissociation of PC-1.0 and PC-1 cells. However, protein expression of Tjp-2 was not affected by DF or U0126 treatment. The current results indicate that Tjp-2 is involved in the regulation of cell dissociation in pancreatic cancer cells through changes in gene expression and intracellular localisation. Tjp-2 may serve as a new target for molecular therapies that prevent the invasion and metastasis of pancreatic cancer.

摘要

高侵袭和转移频率是胰腺癌的关键特征之一。在我们最近的研究中,通过cDNA微阵列分析,紧密连接蛋白2(Tjp-2)被鉴定为在高侵袭性和转移性(PC-1.0)及低侵袭性和转移性(PC-1)胰腺癌细胞中与侵袭转移相关的差异表达基因。紧密连接的结构和功能变化与致癌作用和肿瘤发展相关。在本研究中,采用逆转录聚合酶链反应(RT-PCR)、蛋白质印迹法和免疫细胞化学法研究Tjp-2的表达和定位与胰腺癌细胞解离之间的相关性。Tjp-2 mRNA和蛋白在PC-1.0和PC-1细胞中差异表达。此外,添加解离因子(DF)或U0126(一种丝裂原活化蛋白激酶/细胞外信号调节激酶(MEK)抑制剂)可显著诱导Tjp-2的mRNA表达、蛋白细胞内定位以及PC-1.0和PC-1细胞的同时解离发生变化。然而,DF或U0126处理对Tjp-2的蛋白表达没有影响。目前的结果表明,Tjp-2通过基因表达和细胞内定位的变化参与胰腺癌细胞解离的调控。Tjp-2可能成为预防胰腺癌侵袭和转移的分子治疗新靶点。

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