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Open Access Research article

Stabilization of mismatch repair gene PMS2 by glycogen synthase kinase 3β is implicated in the treatment of cervical carcinoma

Yuan Zhang1*, Yi Min Shu2, Shu Fang Wang3, Bang Hong Da1, Ze Hua Wang1 and Hua Bin Li24*

Author Affiliations

1 Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, PR China

2 Allergy and Cancer Center, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, PR China

3 Department of Pathology, Baylor College of Medicine, Houston, TX 77030, USA

4 Department of Medicine, Feinberg Medical School, Northwestern University, Chicago, IL 60611, USA

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BMC Cancer 2010, 10:58  doi:10.1186/1471-2407-10-58

Published: 23 February 2010

Abstract

Background

PMS2 expression loss was reported in a variety of human. However, its importance has not been fully understood in cervical carcinoma. The aim of this study was to determine the expression of PMS2 in cervical carcinoma and evaluate the significance of mismatch repair gene PMS2 regulated by glycogen synthase kinase 3β (GSK-3β) in chemosensitivity.

Methods

We examined PMS2 and phosphorylated GSK-3β(s9) expression in cervical carcinoma tissues using immunohistochemical staining. Furthermore, we detected PMS2 expression in HeLa cells and evaluate the interaction with GSK-3β after transfection with GSK-3β by small interference RNA (siRNA), co-immunoprecipitation and immunoblotting. We also evaluated the effect of PMS2 transfection on HeLa cells' chemosensitivity to cisplatin treatment.

Results

We found significant downregulation of PMS2 in cervical carcinoma, which was negatively associated with phosphorylated GSK-3β (s9). Furthermore, we demonstrated GSK-3β transfection was able to interact with PMS2 and enhance PMS2 production in HeLa cells, and increased PMS2 production was responsible for enhanced chemosensitivity.

Conclusions

Our results provide the evidence that stabilization of PMS2 production by GSK-3β was important to improve chemosensitization, indicating the significance of GSK-3β-related PMS2 downregulation in the development of cervical carcinoma and in developing a potential strategy for chemotherapy.