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

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...

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Autores principales: Cho, Yu Jin, Kim, Ji Hun, Yoon, Jiyeon, Cho, Sung Jin, Ko, Young San, Park, Jong-Wan, Lee, Hye Seung, Lee, Hee Eun, Kim, Woo Ho, Lee, Byung Lan
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2928182/
https://www.ncbi.nlm.nih.gov/pubmed/20704706
http://dx.doi.org/10.1186/1471-230X-10-91
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author Cho, Yu Jin
Kim, Ji Hun
Yoon, Jiyeon
Cho, Sung Jin
Ko, Young San
Park, Jong-Wan
Lee, Hye Seung
Lee, Hee Eun
Kim, Woo Ho
Lee, Byung Lan
author_facet Cho, Yu Jin
Kim, Ji Hun
Yoon, Jiyeon
Cho, Sung Jin
Ko, Young San
Park, Jong-Wan
Lee, Hye Seung
Lee, Hee Eun
Kim, Woo Ho
Lee, Byung Lan
author_sort Cho, Yu Jin
collection PubMed
description 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 Tyr(216 )(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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spelling pubmed-29281822010-08-26 Constitutive activation of glycogen synthase kinase-3β correlates with better prognosis and cyclin-dependent kinase inhibitors in human gastric cancer Cho, Yu Jin Kim, Ji Hun Yoon, Jiyeon Cho, Sung Jin Ko, Young San Park, Jong-Wan Lee, Hye Seung Lee, Hee Eun Kim, Woo Ho Lee, Byung Lan BMC Gastroenterol Research Article 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 Tyr(216 )(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. BioMed Central 2010-08-12 /pmc/articles/PMC2928182/ /pubmed/20704706 http://dx.doi.org/10.1186/1471-230X-10-91 Text en Copyright ©2010 Cho et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Cho, Yu Jin
Kim, Ji Hun
Yoon, Jiyeon
Cho, Sung Jin
Ko, Young San
Park, Jong-Wan
Lee, Hye Seung
Lee, Hee Eun
Kim, Woo Ho
Lee, Byung Lan
Constitutive activation of glycogen synthase kinase-3β correlates with better prognosis and cyclin-dependent kinase inhibitors in human gastric cancer
title Constitutive activation of glycogen synthase kinase-3β correlates with better prognosis and cyclin-dependent kinase inhibitors in human gastric cancer
title_full Constitutive activation of glycogen synthase kinase-3β correlates with better prognosis and cyclin-dependent kinase inhibitors in human gastric cancer
title_fullStr Constitutive activation of glycogen synthase kinase-3β correlates with better prognosis and cyclin-dependent kinase inhibitors in human gastric cancer
title_full_unstemmed Constitutive activation of glycogen synthase kinase-3β correlates with better prognosis and cyclin-dependent kinase inhibitors in human gastric cancer
title_short Constitutive activation of glycogen synthase kinase-3β correlates with better prognosis and cyclin-dependent kinase inhibitors in human gastric cancer
title_sort constitutive activation of glycogen synthase kinase-3β correlates with better prognosis and cyclin-dependent kinase inhibitors in human gastric cancer
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2928182/
https://www.ncbi.nlm.nih.gov/pubmed/20704706
http://dx.doi.org/10.1186/1471-230X-10-91
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