Format

Send to

Choose Destination
Biochim Biophys Acta. 2014 Sep;1843(9):2079-88. doi: 10.1016/j.bbamcr.2014.05.017. Epub 2014 Jun 4.

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

Author information

1
Laboratory of Biochemistry, Department of Biopharmaceutical Sciences, Gifu Pharmaceutical University, Gifu, Japan; School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan. Electronic address: ikari@gifu-pu.ac.jp.
2
School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan.
3
Laboratory of Biochemistry, Department of Biopharmaceutical Sciences, Gifu Pharmaceutical University, Gifu, Japan.

Abstract

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 S 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.

KEYWORDS:

Adenocarcinoma; Cell proliferation; Claudin-2; Nuclear distribution

PMID:
24907662
DOI:
10.1016/j.bbamcr.2014.05.017
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center