title: Phosphatase activity of nuclear PTEN is required for CDX2-mediated intestinal differentiation of gastric carcinoma.
abstract: The PTEN tumor suppressor localizes predominantly to the cytoplasm, where it negatively regulates the phosphatidylinositol 3-kinase-AKT signaling pathway; however, the biological significance of nuclear PTEN in gastric carcinoma (GC) remains unknown. In this study, transduction of recombinant PTEN into GC-derived TMK-1 cells promoted PTEN nuclear localization with increased mRNA levels of CDX2 and intestinal claudins (CLDN3 and CLDN4), whereas the G129E phosphatase 'dead' mutant had no effect. In GC tissue samples, tumors with nuclear PTEN expression frequently demonstrated the intestinal-type claudin phenotype. Our results suggested that nuclear localization of PTEN is important for determining intestinal differentiation of GCs.
authors.affiliation: Division of Pathology, Department of Pathology and Microbiology, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan. semba@med.kobe-u.ac.jp
authors.forename: Shuho
authors.initials: S
authors.lastname: Semba
authors.forename: Shinya
authors.initials: S
authors.lastname: Satake
authors.forename: Mai
authors.initials: M
authors.lastname: Matsushita
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yokozaki
mesh_terms: D015153:Blotting, Western; D000071616:CDX2 Transcription Factor; D002454:Cell Differentiation; D002467:Cell Nucleus / Q000378:metabolism; D047369:Chromatin Immunoprecipitation; D062445:Claudin-1; D003593:Cytoplasm; D005455:Fluorescent Antibody Technique; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000473:pathology*; D008565:Membrane Proteins / Q000378:metabolism; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D014162:Transfection; D014407:Tumor Cells, Cultured
chemical_list: D000071616:CDX2 Transcription Factor; C491270:CDX2 protein, human; C568108:CLDN1 protein, human; D062445:Claudin-1; D018398:Homeodomain Proteins; D008565:Membrane Proteins; D012333:RNA, Messenger; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human