Involvement of the expression and redistribution of claudin-23 in pancreatic cancer cell dissociation.
Involvement of the expression and redistribution of claudin-23 in pancreatic cancer cell dissociation.
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DOI：
10.3892/mmr.2010.334
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发表时间：
2010-09
影响因子：
3.4
通讯作者：
W. Wang;X. Tan;Lei Zhou;F. Gao;X. Dai
中科院分区：
文献类型：
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作者：
W. Wang;X. Tan;Lei Zhou;F. Gao;X. Dai
胰腺癌细胞从原发部位解离是肿瘤侵袭和转移的关键第一步。据报道，紧密连接的结构和功能的变化与癌变和肿瘤发展相关。利用cDNA微阵列分析，我们最近确定了claudin-23作为一个差异表达的基因相关的高（PC-1.0）和弱（PC-1）侵袭性和转移性胰腺癌细胞的侵袭转移。本研究采用RT-PCR、Western blotting和免疫细胞化学等方法研究了claudin-23在胰腺癌细胞中的表达和分布。Claudin-23 mRNA和蛋白在PC-1.0和PC-1细胞中差异表达。在表达促分裂原活化蛋白激酶激酶（MEK）-1短发夹RNA（shRNA）的PC-1.0亚克隆中诱导紧密连接蛋白-23表达，并且在表达MEK 2 shRNA的PC-1.0亚克隆中重新分布紧密连接蛋白-23。此外，这些表达MEK 2 shRNA的PC-1.0细胞聚集并形成岛状细胞集落。相比之下，解离因子条件培养基的加入显著降低了PC-1细胞中claudin-23 mRNA和蛋白的表达。目前的结果表明，claudin-23是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节。此外，claudin-23的表达可能与胰腺癌细胞解离过程中MEK信号通路的激活相关。Claudin-23可能成为胰腺癌侵袭转移分子治疗的新靶点。
Dissociation of pancreatic cancer cells from primary sites is the critical first step in tumour invasion and metastasis. Changes in the structure and function of tight junctions are reported to be correlated with carcinogenesis and tumour development. Using cDNA microarray analysis, we recently identified claudin-23 as a differentially expressed gene related to invasion-metastasis in highly (PC-1.0) and weakly (PC-1) invasive and metastatic pancreatic cancer cells. In this study, RT-PCR, Western blotting and immunocytochemistry were used to demonstrate the involvement of the expression and redistribution of claudin-23 in pancreatic cancer cell dissociation. Claudin-23 mRNA and protein were differentially expressed in PC-1.0 and PC-1 cells. Claudin-23 expression was induced in a PC-1.0 subclone expressing mitogen-activated protein kinase kinase (MEK)-1 short-hairpin RNA (shRNA) and claudin-23 was redistributed in a PC-1.0 subclone expressing MEK2 shRNA. Furthermore, these MEK2 shRNA-expressing PC-1.0 cells aggregated and formed island-like cell colonies. By contrast, the addition of dissociation factor-conditioned medium significantly reduced claudin-23 mRNA and protein expression in PC-1 cells. The present results indicate that claudin-23 is involved in the regulation of pancreatic cancer cell dissociation through changes in gene expression and intracellular localisation. In addition, claudin-23 expression is possibly correlated with the activation of the MEK signalling pathway during pancreatic cancer cell dissociation. Claudin-23 may thus serve as a new target for molecular therapies to prevent pancreatic cancer invasion and metastasis.