Regulation of tight junctions in human normal pancreatic duct epithelial cells and cancer cells
Regulation of tight junctions in human normal pancreatic duct epithelial cells and cancer cells
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DOI：
10.1111/j.1749-6632.2012.06579.x
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发表时间：
2012-01-01
期刊：
影响因子：
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通讯作者：
Sawada, Norimasa
中科院分区：
文献类型：
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作者：
Kojima, Takashi;Sawada, Norimasa
为了研究紧密连接分子在正常人胰腺管上皮(HPDE)细胞和胰腺癌细胞中的调控作用，我们将人端粒酶逆转录酶(HTERT)基因导入原代培养的HPDE细胞，并与胰腺癌细胞系进行了比较。HTERT转染的HPDE细胞呈PDE标志物阳性，表达claudin-1、claudin-4、claudin-7、claudin-18、occludin、tricellin、marvelD3、JAM-A、ZO-1和ZO-2。正常HPDE细胞的紧密连接分子，包括claudin-4和claudin-18，部分通过转录调控的蛋白激酶C信号通路进行调节。此外，正常HPDE细胞和胰腺癌细胞中的claudin-18可被PKC激活剂显著诱导，胰腺癌细胞中的claudin-18也可被DNA甲基化修饰。在正常HPDE细胞和胰腺癌细胞的Marvel家族中，在蜗牛诱导的上皮-间充质转化过程中，三细胞蛋白通过c-jun氨基末端激酶途径上调，marvelD3下调。
To investigate the regulation of tight junction molecules in normal human pancreatic duct epithelial (HPDE) cells and pancreatic cancer cells, we introduced the human telomerase reverse transcriptase (hTERT) gene into HPDE cells in primary culture and compared them to pancreatic cancer cell lines. The hTERT-transfected HPDE cells were positive for PDE markers and expressed claudin-1, claudin-4, claudin-7, and claudin-18, occludin, tricellulin, marvelD3, JAM-A, zonula occludens (ZO)-1, and ZO-2. The tight junction molecules, including claudin-4 and claudin-18 of normal HPDE cells, were in part regulated via a protein kinase C signal pathway by transcriptional control. In addition, claudin-18 in normal HPDE cells and pancreatic cancer cells was markedly induced by a PKC activator, and claudin-18 in pancreatic cancer cells was also modified by DNA methylation. In the marvel family of normal HPDE cells and pancreatic cancer cells, tricellulin was upregulated via a c-Jun N-terminal kinase pathway, and marvelD3 was downregulated during Snail-induced epithelial-mesenchymal transition.