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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...
Autores principales: | , , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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BioMed Central
2010
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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. |
format | Text |
id | pubmed-2928182 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
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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