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

Cited 16 time in Web of Science Cited 20 time in Scopus
Authors
Cho, Yu Jin; Kim, Ji Hun; Yoon, Jiyeon; Cho, Sung Jin; Park, Jong-Wan; Lee, Hee Eun; Lee, Byung Lan; Kim, Woo Ho; Lee, Hye Seung; Ko, Young San
Issue Date
2010-08-12
Publisher
BIOMED CENTRAL LTD
Citation
BMC GASTROENTEROLOGY; Vol.10; 91
Abstract
Background: Aberrant regulation of glycogen synthase kinase-3 beta (GSK-3 beta) 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-3 beta phosphorylated at Tyr(216) (pGSK-3 beta) 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-3 beta inhibitor lithium chloride (LiCl) for immunoblot analysis. Results: We found that pGSK-3 beta 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-3 beta 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-3 beta expression positively correlated with that of p16, p21, p27, p53, APC, PTEN, MGMT, SMAD4, or KAl1 (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-3 beta activation was frequently observed in early-stage gastric carcinoma and was significantly correlated with better prognosis. Thus, these findings suggest that GSK-3 beta activation is a useful prognostic marker for the early-stage gastric cancer.
ISSN
1471-230X
Language
English
URI
http://hdl.handle.net/10371/78663
DOI
https://doi.org/10.1186/1471-230X-10-91
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College of Medicine/School of Medicine (의과대학/대학원)Anatomy (해부학전공)Journal Papers (저널논문_해부학전공)
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