Glycogen synthase kinase-3β does not correlate with the expression and activity of β-catenin in gastric cancer.
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.
Cho
Yu-Jin
YJ
Departments of Anatomy, Medical Research Center, Seoul National University College of Medicine, Seoul, Korea.
Yoon
Jiyeon
J
Ko
Young-San
YS
Kim
Sue-Youn
SY
Cho
Sung-Jin
SJ
Kim
Woo-Ho
WH
Park
Jong-Wan
JW
Youn
Hong-Duk
HD
Kim
Ji-Hun
JH
Lee
Byung-Lan
BL
D015153:Blotting, Western; D045744:Cell Line, Tumor; D016009:Chi-Square Distribution; D004789:Enzyme Activation / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D007150:Immunohistochemistry; D018021:Lithium Chloride / Q000494:pharmacology; D013274:Stomach Neoplasms / Q000201:enzymology / Q000378:metabolism*; D046888:Tissue Array Analysis; D051176:beta Catenin / Q000096:biosynthesis / Q000378:metabolism*
D004791:Enzyme Inhibitors; D051176:beta Catenin; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3; D018021:Lithium Chloride