Knockdown of CRM1 inhibits the nuclear export of p27(Kip1) phosphorylated at serine 10 and plays a role in the pathogenesis of epithelial ovarian cancer

You Wang; Yingying Wang; Jingying Xiang; Fang Ji; Yan Deng; Chunhui Tang; Shuyun Yang; Qinghua Xi; Rong Liu; Wen Di

doi:10.1016/j.canlet.2013.09.002

Knockdown of CRM1 inhibits the nuclear export of p27(Kip1) phosphorylated at serine 10 and plays a role in the pathogenesis of epithelial ovarian cancer

Cancer Lett. 2014 Feb 1;343(1):6-13. doi: 10.1016/j.canlet.2013.09.002. Epub 2013 Sep 7.

Authors

You Wang¹, Yingying Wang², Jingying Xiang³, Fang Ji⁴, Yan Deng², Chunhui Tang², Shuyun Yang², Qinghua Xi², Rong Liu⁵, Wen Di⁶

Affiliations

¹ Department of Obstetrics and Gynecology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200001, PR China; Department of Obstetrics and Gynecology, Wuxi Maternal and Child Health Hospital, Nanjing Medical University, Wuxi 214000, PR China.
² Department of Obstetrics and Gynecology, Nantong University Cancer Hospital, Nantong University, Nantong 226001, Jiangsu, PR China.
³ Department of Obstetrics and Gynecology, Wuxi Maternal and Child Health Hospital, Nanjing Medical University, Wuxi 214000, PR China.
⁴ Department of Obstetrics and Gynecology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200001, PR China.
⁵ Department of Obstetrics and Gynecology, Nantong University Cancer Hospital, Nantong University, Nantong 226001, Jiangsu, PR China. Electronic address: [email protected].
⁶ Department of Obstetrics and Gynecology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200001, PR China. Electronic address: [email protected].

PMID: 24018641
DOI: 10.1016/j.canlet.2013.09.002

Abstract

In a previous study, the nuclear export protein chromosomal region maintenance (CRM1) was correlated with p27(Kip1) in glioma. The aims of the present study were to investigate the expression of CRM1 and pSer10p27 and their functional roles in epithelial ovarian cancer (EOC) tissues. Using immunohistochemical analysis, CRM1 and pSer10p27 expression levels were shown to be associated with histologic stage and grade (P<0.05). High CRM1 and pSer10p27 expression levels were prognostic indicators of overall survival (P<0.05). Knockdown of CRM1 and pSer10p27 expression arrested cell cycle progression and inhibited the proliferation of SKOV3 cells both in vitro and in vivo. These data support the idea that pSer10p27 and CRM1 play cooperative roles in EOC.

Keywords: Chromosomal region maintenance; Epithelial ovarian cancer; Phosphorylation; Proliferation; p27(Kip1).

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Active Transport, Cell Nucleus
Adult
Animals
Carcinoma, Ovarian Epithelial
Cell Line, Tumor
Cell Proliferation
Cyclin-Dependent Kinase Inhibitor p27 / metabolism*
Exportin 1 Protein
Female
Gene Expression Profiling
Gene Expression Regulation, Neoplastic*
Gene Knockdown Techniques
Humans
Immunohistochemistry
Karyopherins / genetics*
Karyopherins / metabolism
Mice
Microscopy, Fluorescence
Middle Aged
Neoplasm Transplantation
Neoplasms, Glandular and Epithelial / genetics*
Neoplasms, Glandular and Epithelial / metabolism
Ovarian Neoplasms / genetics*
Ovarian Neoplasms / metabolism
Phosphorylation
Receptors, Cytoplasmic and Nuclear / genetics*
Receptors, Cytoplasmic and Nuclear / metabolism
Serine / chemistry

Substances

CDKN1B protein, human
Karyopherins
Receptors, Cytoplasmic and Nuclear
Cyclin-Dependent Kinase Inhibitor p27
Serine