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BMC Gastroenterology
Published in: BMC Gastroenterology 1/2010

Open Access 01-12-2010 | Research article

Constitutive activation of glycogen synthase kinase-3β correlates with better prognosis and cyclin-dependent kinase inhibitors in human gastric cancer

Authors: Yu Jin Cho, Ji Hun Kim, Jiyeon Yoon, Sung Jin Cho, Young San Ko, Jong-Wan Park, Hye Seung Lee, Hee Eun Lee, Woo Ho Kim, Byung Lan Lee

Published in: BMC Gastroenterology | Issue 1/2010

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Abstract

Background

Aberrant regulation of glycogen synthase kinase-3β (GSK-3β) has been implicated in several human cancers; however, it has not been reported in the gastric cancer tissues to date. The present study was performed to determine the expression status of active form of GSK-3β phosphorylated at Tyr216 (pGSK-3β) and its relationship with other tumor-associated proteins in human gastric cancers.

Methods

Immunohistochemistry was performed on tissue array slides containing 281 human gastric carcinoma specimens. In addition, gastric cancer cells were cultured and treated with a GSK-3β inhibitor lithium chloride (LiCl) for immunoblot analysis.

Results

We found that pGSK-3β was expressed in 129 (46%) of 281 cases examined, and was higher in the early-stages of pathologic tumor-node-metastasis (P < 0.001). The expression of pGSK-3β inversely correlated with lymphatic invasion (P < 0.001) and lymph node metastasis (P < 0.001) and correlated with a longer patient survival (P < 0.001). In addition, pGSK-3β expression positively correlated with that of p16, p21, p27, p53, APC, PTEN, MGMT, SMAD4, or KAI1 (P < 0.05), but not with that of cyclin D1. This was confirmed by immunoblot analysis using SNU-668 gastric cancer cells treated with LiCl.

Conclusions

GSK-3β activation was frequently observed in early-stage gastric carcinoma and was significantly correlated with better prognosis. Thus, these findings suggest that GSK-3β activation is a useful prognostic marker for the early-stage gastric cancer.
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Metadata
Title
Constitutive activation of glycogen synthase kinase-3β correlates with better prognosis and cyclin-dependent kinase inhibitors in human gastric cancer
Authors
Yu Jin Cho
Ji Hun Kim
Jiyeon Yoon
Sung Jin Cho
Young San Ko
Jong-Wan Park
Hye Seung Lee
Hee Eun Lee
Woo Ho Kim
Byung Lan Lee
Publication date
01-12-2010
Publisher
BioMed Central
Published in
BMC Gastroenterology / Issue 1/2010
Electronic ISSN: 1471-230X
DOI
https://doi.org/10.1186/1471-230X-10-91

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