Analysis of invasion-metastasis mechanism in pancreatic cancer: Involvement of tight junction transmembrane protein occludin and MEK/ERK signal transduction pathway in cancer cell dissociation

被引：24

作者：

Tan, XD ^{[1
]}

Tamori, Y ^{[1
]}

Egami, H ^{[1
]}

Ishikawa, S ^{[1
]}

Kurizaki, T ^{[1
]}

Takai, E ^{[1
]}

Hirota, M ^{[1
]}

Ogawa, M ^{[1
]}

机构：

[1] Kumamoto Univ, Sch Med, Dept Surg 2, Kumamoto 8608556, Japan

来源：

ONCOLOGY REPORTS | 2004年 / 11卷 / 05期

关键词：

occludin; mitogen-activated protein kinase kinase; extracellular signal regulated kinase; cell dissociation; pancreatic cancer;

D O I：

暂无

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

Mitogen-activated protein kinase kinase 2 (MEK2) was detected as an invasion-metastasis related factor between highly invasive (PC-1.0) and weakly invasive (PC-1) pancreatic cancer cell lines in our previous study. On the other hand, tight junction (TJ) was found to be correlated with carcinogenesis and tumor development. In this study, the expressions and correlation of TJ transmembrane protein occludin and MEK/extracellular signal-regulated kinase (ERK) signaling pathway were analyzed to clarify the regulatory mechanism of cell dissociation in pancreatic cancer cells. Two hamster (PC-1.0 and PC-1) and human (AsPC-1 and CAPAN-2) pancreatic cancer cell lines were analyzed immunocytochemically with anti-occludin, phosphorylated MEK1/2 (pMEK1/2), phosphorylated ERK1/2 (p-ERK1/2) antibodies. MEK1/2 inhibitor U0126 significantly induced the expression of occludin at the cell-cell junction and substantially suppressed the p-MEK1/2 and p-ERK1/2 expressions in PC-1.0 and AsPC-1 cells. In contrast, dissociation factor (DF) treatment obviously disrupted the occludin expressions at the sites of cell-cell junction and markedly induced the pMEK1/2 and p-ERK1/2 expressions in PC-1 and CAPAN-2 cells. In addition, occludin expressions at cell-cell junction were restored and p-MEK1/2 and p-ERK1/2 expressions were suppressed by subsequent U0126-treatment in DF treated PC-1 and CAPAN-2 cells. Correspondingly, light microscopic images showed that DF induced the dissociation of cell island-like colonies in PC-1 and CAPAN-2 cells, and U0126-treatment induced cell aggregation in these pancreatic cancer cells. Occludin is involved in the cell dissociation in pancreatic cancer cells. Moreover, MEK/ERK signaling pathway probably regulates the cell dissociation status of pancreatic cancer through influencing the intracellular localization and expression of occludin.

引用

页码：993 / 998

页数：6

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