We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Constitutive activation of glycogen synthase kinase-3beta correlates with better prognosis and cyclin-dependent kinase inhibitors in human gastric cancer.
- Authors
Cho YJ; Kim JH; Yoon J; Cho SJ; Ko YS; Park JW; Lee HS; Lee HE; Kim WH; Lee BL; 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
- Abstract
<bold>Background: </bold>Aberrant regulation of glycogen synthase kinase-3beta (GSK-3beta) 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-3beta phosphorylated at Tyr216 (pGSK-3beta) and its relationship with other tumor-associated proteins in human gastric cancers.<bold>Methods: </bold>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-3beta inhibitor lithium chloride (LiCl) for immunoblot analysis.<bold>Results: </bold>We found that pGSK-3beta 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-3beta 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-3beta 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.<bold>Conclusions: </bold>GSK-3beta activation was frequently observed in early-stage gastric carcinoma and was significantly correlated with better prognosis. Thus, these findings suggest that GSK-3beta activation is a useful prognostic marker for the early-stage gastric cancer.
- Publication
BMC Gastroenterology, 2010, Vol 10, p91
- ISSN
1471-230X
- Publication type
journal article
- DOI
10.1186/1471-230X-10-91