Glycogen synthase kinase-3β does not correlate with the expression and activity of β-catenin in gastric cancer

The regulation of beta-catenin activation by glycogen synthase kinase-3 beta (GSK-3 beta) in cancer has been shown to be cell type-specific. This study was performed to investigate the relationship between activated GSK-3 beta (phosphorylated at Tyr216) and beta-catenin in gastric cancer. Immunohistochemical tissue array analysis of 278 human gastric carcinoma specimens showed positive immunoreactivity for activated GSK-3 beta in 44% of the samples, whereas membranous beta-catenin and nuclear beta-catenin were observed in 19% and 20% of the samples, respectively. However, GSK-3 beta activation was not correlated with the expression of either membranous beta-catenin or nuclear beta-catenin. Moreover, SNU gastric cancer cell lines over-expressing kinase dead GSK-3 beta and the same cells treated with a GSK-3 beta inhibitor showed that GSK-3 beta inhibition did not alter either the protein expression or transcriptional activity of beta-catenin. In addition, GSK-3 beta activation was positively correlated with the expressions of anti-adenomatous polyposis coli (p = 0.002), p16 (p < 0.001), p21 (p < 0.001), p27 (p = 0.001), and p53 (p = 0.013). On the other hand, the nuclear expression of beta-catenin was positively correlated with those of Bcl-2 (p = 0.025) and cyclin D1 (p = 0.043), but these expressions were not correlated with GSK-3 beta activation. Thus, the GSK-3 beta pathway seems to function in gastric cancer cells without involving the beta-catenin pathway.