title: Multinuclear giant cell formation is enhanced by down-regulation of Wnt signaling in gastric cancer cell line, AGS.
abstract: AGS cells, which were derived from malignant gastric adenocarcinoma tissue, lack E-cadherin-mediated cell adhesion but have a high level of nuclear beta-catenin, which suggests altered Wnt signal. In addition, approximately 5% of AGS cells form multinuclear giant cells in the routine culture conditions, while taxol treatment causes most AGS cells to become giant cells. The observation of reduced nuclear beta-catenin levels in giant cells induced by taxol treatment prompted us to investigate the relationship between Wnt signaling and giant cell formation. After overnight serum starvation, the shape of AGS cells became flattened, and this morphological change was accompanied by decrease in Myc expression and an increase in the giant cell population. Lithium chloride treatment, which inhibits GSK3beta activity, reversed these serum starvation effects, which suggests an inverse relationship between Wnt signaling and giant cell formation. Furthermore, the down-regulation of Wnt signaling caused by the over-expression of ICAT, E-cadherin, and Axin enhanced giant cell formation. Therefore, down-regulation of Wnt signaling may be related to giant cell formation, which is considered to be a survival mechanism against induced cell death.
authors.affiliation: Laboratory of Epithelial Cell Biology, Department of Microbiology, College of Medicine, Korea University, 126-1, Anam-5-ga, Sungbuk-gu, Seoul 136-705, Republic of Korea.
authors.forename: Shi-Mun
authors.initials: SM
authors.lastname: Kim
authors.forename: Rockki
authors.initials: R
authors.lastname: Kim
authors.forename: Jae-Hyun
authors.initials: JH
authors.lastname: Ryu
authors.forename: Eek-Hoon
authors.initials: EH
authors.lastname: Jho
authors.forename: Ki-Joon
authors.initials: KJ
authors.lastname: Song
authors.forename: Shyh-Ing
authors.initials: SI
authors.lastname: Jang
authors.forename: Sun-Ho
authors.initials: SH
authors.lastname: Kee
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015820:Cadherins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D002452:Cell Count; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D048430:Cell Shape / Q000187:drug effects; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D003598:Cytoskeletal Proteins / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D015726:Giant Cells / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015534:Trans-Activators / Q000378:metabolism; D051153:Wnt Proteins; D051176:beta Catenin
chemical_list: C495270:CTNNB1 protein, human; D015820:Cadherins; D016895:Culture Media, Serum-Free; D003598:Cytoskeletal Proteins; D036341:Intercellular Signaling Peptides and Proteins; D015534:Trans-Activators; D051153:Wnt Proteins; D051176:beta Catenin