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

Abstract

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. 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. 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. 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.
Authors:
Zhang, Yuan; [1]  Shu, Yi Min; [2]  Wang, Shu Fang; [3]  Da, Bang Hong; Wang, Ze Hua; [1]  Li, Hua Bin; [2]  Department of Medicine, Feinberg Medical School, Northwestern University, Chicago, IL 60611 (United States)]
  1. Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022 (China)
  2. Allergy and Cancer Center, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080 (China)
  3. Department of Pathology, Baylor College of Medicine, Houston, TX 77030 (United States)
Publication Date:
Feb 23, 2010
Product Type:
Journal Article
Resource Relation:
Journal Name: BMC Cancer (Online); Journal Volume: 10; Other Information: PMCID: PMC2843672; PUBLISHER-ID: 1471-2407-10-58; PMID: 20178594; OAI: oai:pubmedcentral.nih.gov:2843672; Copyright (c)2010 Zhang et al; licensee BioMed Central Ltd.; This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0) (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.; Country of input: International Atomic Energy Agency (IAEA)
Subject:
60 APPLIED LIFE SCIENCES; 62 RADIOLOGY AND NUCLEAR MEDICINE; CARCINOMAS; CHEMOTHERAPY; GENES; GLYCOGEN; HELA CELLS; INTERACTIONS; INTERFERENCE; LOSSES; POTENTIALS; RNA; STABILIZATION
OSTI ID:
22387578
Country of Origin:
United Kingdom
Language:
English
Other Identifying Numbers:
Journal ID: ISSN 1471-2407; TRN: GB15$3271093187
Availability:
Available from http://dx.doi.org/10.1186/1471-2407-10-58; Available from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2843672
Submitting Site:
INIS
Size:
page(s) 58
Announcement Date:
Oct 22, 2015

Citation Formats

Zhang, Yuan, Shu, Yi Min, Wang, Shu Fang, Da, Bang Hong, Wang, Ze Hua, Li, Hua Bin, and Department of Medicine, Feinberg Medical School, Northwestern University, Chicago, IL 60611 (United States)]. Stabilization of mismatch repair gene PMS2 by glycogen synthase kinase 3β is implicated in the treatment of cervical carcinoma. United Kingdom: N. p., 2010. Web. doi:10.1186/1471-2407-10-58.
Zhang, Yuan, Shu, Yi Min, Wang, Shu Fang, Da, Bang Hong, Wang, Ze Hua, Li, Hua Bin, & Department of Medicine, Feinberg Medical School, Northwestern University, Chicago, IL 60611 (United States)]. Stabilization of mismatch repair gene PMS2 by glycogen synthase kinase 3β is implicated in the treatment of cervical carcinoma. United Kingdom. doi:10.1186/1471-2407-10-58.
Zhang, Yuan, Shu, Yi Min, Wang, Shu Fang, Da, Bang Hong, Wang, Ze Hua, Li, Hua Bin, and Department of Medicine, Feinberg Medical School, Northwestern University, Chicago, IL 60611 (United States)]. 2010. "Stabilization of mismatch repair gene PMS2 by glycogen synthase kinase 3β is implicated in the treatment of cervical carcinoma." United Kingdom. doi:10.1186/1471-2407-10-58. https://www.osti.gov/servlets/purl/10.1186/1471-2407-10-58.
@misc{etde_22387578,
title = {Stabilization of mismatch repair gene PMS2 by glycogen synthase kinase 3β is implicated in the treatment of cervical carcinoma}
author = {Zhang, Yuan, Shu, Yi Min, Wang, Shu Fang, Da, Bang Hong, Wang, Ze Hua, Li, Hua Bin, and Department of Medicine, Feinberg Medical School, Northwestern University, Chicago, IL 60611 (United States)]}
abstractNote = {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. 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. 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. 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.}
doi = {10.1186/1471-2407-10-58}
journal = {BMC Cancer (Online)}
volume = {10}
journal type = {AC}
place = {United Kingdom}
year = {2010}
month = {Feb}
}