Nuclear distribution of claudin-2 increases cell proliferation in human lung adenocarcinoma cells

被引：76

作者：

Ikari, Akira ^{[1
,2
]}

Watanabe, Ryo ^{[2
]}

Sato, Tomonari ^{[2
]}

Taga, Saeko ^{[1
]}

Shimobaba, Shun ^{[1
]}

Yamaguchi, Masahiko ^{[2
]}

Yamazaki, Yasuhiro ^{[2
]}

Endo, Satoshi ^{[1
]}

Matsunaga, Toshiyuki ^{[1
]}

Sugatani, Junko ^{[2
]}

机构：

[1] Gifu Pharmaceut Univ, Dept Biopharmaceut Sci, Biochem Lab, Gifu 5011196, Japan

[2] Univ Shizuoka, Sch Pharmaceut Sci, Shizuoka 4228526, Japan

来源：

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH | 2014年 / 1843卷 / 09期

关键词：

Adenocarcinoma; Claudin-2; Cell proliferation; Nuclear distribution; CYCLIN D1; PANCREATIC-CANCER; TIGHT JUNCTIONS; BREAST-CANCER; COLON-CANCER; EXPRESSION; PROTEIN; CARCINOMA; PHOSPHORYLATION; TUMORIGENICITY;

D O I：

10.1016/j.bbamcr.2014.05.017

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Claudin-2 is expressed in human lung adenocarcinoma tissue and cell lines, although it is absent in normal lung tissue. However, the role of claudin-2 in cell proliferation and the regulatory mechanism of intracellular distribution remain undefined. Proliferation of human adenocarcinoma A549 cells was decreased by claudin-2 knockdown together with a decrease in the percentage of S phase cells. This knockdown decreased the expression levels of ZONAB and cell cycle regulators. Claudin-2 was distributed in the nucleus in human adenocarcinoma tissues and proliferating A549 cells. The nuclear distribution of ZONAB and percentage of phase cells were higher in cells exogenously expressing claudin-2 with a nuclear localization signal than in cells expressing claudin-2 with a nuclear export signal. Nuclear claudin-2 formed a complex with ZO-1, ZONAB, and cyclin D1. Nuclear distribution of S208A mutant, a dephosphorylated form of claudin-2, was higher than that of wild type. We suggest that nuclear distribution of claudin-2 is up-regulated by dephosphorylation and claudin-2 serves to retain ZONAB and cyclin D1 in the nucleus, resulting in the enhancement of cell proliferation in lung adenocarcinoma cells. (C) 2014 Elsevier B.V. All rights reserved.

引用

页码：2079 / 2088

页数：10

共 43 条

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