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

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Abstract:

Cho Y-J, Yoon J, Ko Y-S, Kim S-Y, Cho S-J, Kim W-H, Park J-W, Youn H-D, Kim J-H, Lee B-L. Glycogen synthase kinase-3β does not correlate with the expression and activity of β-catenin in gastric cancer. APMIS 2010; 118: 782–90.

The regulation of β-catenin activation by glycogen synthase kinase-3β (GSK-3β) in cancer has been shown to be cell type-specific. This study was performed to investigate the relationship between activated GSK-3β (phosphorylated at Tyr216) and β-catenin in gastric cancer. Immunohistochemical tissue array analysis of 278 human gastric carcinoma specimens showed positive immunoreactivity for activated GSK-3β in 44% of the samples, whereas membranous β-catenin and nuclear β-catenin were observed in 19% and 20% of the samples, respectively. However, GSK-3β activation was not correlated with the expression of either membranous β-catenin or nuclear β-catenin. Moreover, SNU gastric cancer cell lines over-expressing kinase dead GSK-3β and the same cells treated with a GSK-3β inhibitor showed that GSK-3β inhibition did not alter either the protein expression or transcriptional activity of β-catenin. In addition, GSK-3β 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 β-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-3β activation. Thus, the GSK-3β pathway seems to function in gastric cancer cells without involving the β-catenin pathway.

Keywords: GSK-3β; gastric carcinoma; immunohistochemistry; tissue microarray; β-catenin

Document Type: Research Article

DOI: http://dx.doi.org/10.1111/j.1600-0463.2010.02659.x

Affiliations: 1: Departments of Anatomy 2: Pathology 3: Pharmacology 4: Biochemistry and Molecular Biology, Medical Research Center, Seoul National University College of Medicine, Seoul 5: Department of Pathology, Asan Medical Center, Ulsan University College of Medicine, Seoul

Publication date: October 1, 2010

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