title: Association of cellular localization of glycogen synthase kinase 3beta in the digestive tract with cancer development.
abstract: Glycogen synthase kinase 3beta (GSK-3beta) is a multifunctional serine/threonine kinase involved in several signaling pathways. Recently, we reported the polarized localization of GSK-3beta on the apical membrane of normal colon epithelium. To investigate the functions of this molecule, we studied stomach and colorectal cancer tissues. In normal simple columnar epithelium, GSK-3beta was localized with tight junction-associated protein ZO-1 in a single line at the apical cell border. GSK-3beta and ZO-1 were localized in the apical regions of tubular adenocarcinoma, similar to their localization in normal epithelium; however, their localization was different at the invasive front of the cancer and was found to be associated with lymphatic invasion. In signet-ring cell carcinoma of the stomach, the expression of these proteins was reduced and dot-like expression was observed in each cell of the signet-ring cell carcinoma. We speculated that GSK-3beta is involved in glandular structure formation and that the non-apical localization of membrane-localized GSK-3beta in tubular adenocarcinoma is associated with cancer development.
authors.affiliation: Department of Tumor and Diagnostic Pathology, Atomic Bomb Disease Institute, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852-8523, Japan. h-hira@nagasaki-u.ac.jpc
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Hirakawa
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Nakayama
authors.forename: Kenichiro
authors.initials: K
authors.lastname: Shibata
authors.forename: Ichiro
authors.initials: I
authors.lastname: Sekine
mesh_terms: D000230:Adenocarcinoma / Q000201:enzymology; D000368:Aged; D003110:Colonic Neoplasms / Q000201:enzymology*; D005260:Female; D017491:Genes, APC; D038362:Glycogen Synthase Kinase 3 / Q000032:analysis* / Q000502:physiology; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000201:enzymology; D008297:Male; D008565:Membrane Proteins / Q000032:analysis; D008875:Middle Aged; D010750:Phosphoproteins / Q000032:analysis; D013274:Stomach Neoplasms / Q000201:enzymology*; D062826:Zonula Occludens-1 Protein
chemical_list: D008565:Membrane Proteins; D010750:Phosphoproteins; C569042:TJP1 protein, human; D062826:Zonula Occludens-1 Protein; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3