Kondo Jun, Sato Fuyuki, Kusumi Tomomi, Liu Yang, Motonari Ohashi, Sato Tatsusuke, Kijima Hiroshi
Department of Pathology and Bioscience, Hirosaki University Graduate School of Medicine, Hirosaki 036-8562, Japan.
Int J Mol Med. 2008 Nov;22(5):645-9.
Claudin-1 is a membrane protein with four transmembrane domains, that is exclusively localized at cellular tight junctions. Recent studies have reported that claudin-1 plays an important role in cancer invasion and metastasis. However, the significance of claudin-1 in pancreatic cancer is still unknown. In the present study, we investigated the role of claudin-1 expression in pancreatic cancer growth using the PANC-1 human pancreatic cancer cell line. Treatment with tumor necrosis factor-alpha (TNF-alpha), an inflammatory cytokine, resulted in increased detection of 89 kDa products of poly-(ADP-ribose) polymerase (PARP), a marker of apoptosis, and decreased PANC-1 cell proliferation by 23%. Expression of claudin-1 was up-regulated by TNF-alpha in a concentration-dependent manner in PANC-1 cells. PANC-1 cells treated with TNF-alpha and siRNA against claudin-1 showed a 15% increase in proliferation; i.e. the cells transfected with siRNA against claudin-1 showed resistance to TNF-alpha-induced apoptosis. These results suggest that claudin-1 expression is responsible for TNF-alpha-dependent growth signals and the proliferation of pancreatic cancer cells.
Claudin-1是一种具有四个跨膜结构域的膜蛋白，仅定位于细胞紧密连接处。最近的研究报道，Claudin-1在癌症侵袭和转移中起重要作用。然而，Claudin-1在胰腺癌中的意义仍不清楚。在本研究中，我们使用PANC-1人胰腺癌细胞系研究了Claudin-1表达在胰腺癌生长中的作用。用肿瘤坏死因子-α（TNF-α）（一种炎性细胞因子）处理后，凋亡标志物聚（ADP-核糖）聚合酶（PARP）89 kDa产物的检测增加，PANC-1细胞增殖减少23%。在PANC-1细胞中，TNF-α以浓度依赖性方式上调Claudin-1的表达。用TNF-α和针对Claudin-1的小干扰RNA（siRNA）处理的PANC-1细胞增殖增加了15%；即转染针对Claudin-1的siRNA的细胞对TNF-α诱导的凋亡具有抗性。这些结果表明，Claudin-1表达负责TNF-α依赖性生长信号和胰腺癌细胞的增殖。
