AP1B plays an important role in intestinal tumorigenesis with the truncating mutation of an APC gene
Mitsuko Mimura
Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan
Search for more papers by this authorAtsuhiro Masuda
Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan
Search for more papers by this authorShin Nishiumi
Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan
Search for more papers by this authorKazuyuki Kawakami
Division of Translational and Clinical Oncology, Cancer Research Institute, Kanazawa University, Kanazawa, Ishikawa, Japan
Search for more papers by this authorYoshimi Fujishima
Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan
Search for more papers by this authorTomoo Yoshie
Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan
Search for more papers by this authorShigeto Mizuno
Department of Medical Pharmaceutics, Kobe Pharmaceutical University, Kobe, Hyogo, Japan
Search for more papers by this authorIkuya Miki
Department of Medical Pharmaceutics, Kobe Pharmaceutical University, Kobe, Hyogo, Japan
Search for more papers by this authorHiroshi Ohno
Laboratory for Epithelial Immunobiology, Research Center for Allergy and Immunology, RIKEN, Kanagawa, Japan
Department of Supramolecular Biology, International Graduate School of Bionanoscience, Yokohama City University, Kanagawa, Japan
Search for more papers by this authorKoji Hase
Laboratory for Epithelial Immunobiology, Research Center for Allergy and Immunology, RIKEN, Kanagawa, Japan
Search for more papers by this authorToshinari Minamoto
Division of Translational and Clinical Oncology, Cancer Research Institute, Kanazawa University, Kanazawa, Ishikawa, Japan
Search for more papers by this authorTakeshi Azuma
Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan
Search for more papers by this authorCorresponding Author
Masaru Yoshida
Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan
Integrated Center for Mass Spectrometry, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan
Division of Metabolomics, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan
Tel: +81-78-382-6305; Fax: +81-78-382-6309
Division of Metabolomics, Integrated Center for Mass Spectrometry, Division of Gastroenterology, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chu-o-ku, Kobe, Hyogo 650-0017, JapanSearch for more papers by this authorMitsuko Mimura
Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan
Search for more papers by this authorAtsuhiro Masuda
Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan
Search for more papers by this authorShin Nishiumi
Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan
Search for more papers by this authorKazuyuki Kawakami
Division of Translational and Clinical Oncology, Cancer Research Institute, Kanazawa University, Kanazawa, Ishikawa, Japan
Search for more papers by this authorYoshimi Fujishima
Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan
Search for more papers by this authorTomoo Yoshie
Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan
Search for more papers by this authorShigeto Mizuno
Department of Medical Pharmaceutics, Kobe Pharmaceutical University, Kobe, Hyogo, Japan
Search for more papers by this authorIkuya Miki
Department of Medical Pharmaceutics, Kobe Pharmaceutical University, Kobe, Hyogo, Japan
Search for more papers by this authorHiroshi Ohno
Laboratory for Epithelial Immunobiology, Research Center for Allergy and Immunology, RIKEN, Kanagawa, Japan
Department of Supramolecular Biology, International Graduate School of Bionanoscience, Yokohama City University, Kanagawa, Japan
Search for more papers by this authorKoji Hase
Laboratory for Epithelial Immunobiology, Research Center for Allergy and Immunology, RIKEN, Kanagawa, Japan
Search for more papers by this authorToshinari Minamoto
Division of Translational and Clinical Oncology, Cancer Research Institute, Kanazawa University, Kanazawa, Ishikawa, Japan
Search for more papers by this authorTakeshi Azuma
Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan
Search for more papers by this authorCorresponding Author
Masaru Yoshida
Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan
Integrated Center for Mass Spectrometry, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan
Division of Metabolomics, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan
Tel: +81-78-382-6305; Fax: +81-78-382-6309
Division of Metabolomics, Integrated Center for Mass Spectrometry, Division of Gastroenterology, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chu-o-ku, Kobe, Hyogo 650-0017, JapanSearch for more papers by this authorAbstract
Recent evidence has suggested that carcinoma is accompanied by the loss of cell polarity. An epithelial cell-specific form of the AP-1 clathrin adaptor complex, AP1B, is involved in the polarized transport of membrane proteins to the basolateral surface of epithelial cells. In our study, we investigated whether AP1B is involved in intestinal tumorigenesis. The cellular polarity of intestinal tumor cells was examined using APCMin/+ mice as an in vivo model and SW480 cells with a truncating mutation in the adenomatous polyposis coli (APC) gene as an in vitro model by confocal microscopy. Next, the expression of AP1B in intestinal tumor cells was examined by real-time polymerase chain reaction (PCR) and Western blotting. The localization of β-catenin and the expression of AP1B in the tumor tissue of patients with colorectal cancer were evaluated by confocal microscopy and real-time PCR, respectively, and the relationships among cell polarity, AP1B expression and intestinal tumorigenesis were examined. Cellular polarity was lost in intestinal tumor cells, and the expression of AP1B was downregulated. In addition, the reduction in the expression level of AP1B correlated with the nuclear localization of β-catenin in human colorectal cancer. Our study indicates the close associations between AP1B, intestinal tumorigenesis and mutations in the APC gene. This is the first report to reveal the relationships among AP1B, cellular polarity and intestinal tumorigenesis, and achieving a detailed understanding of AP1B will hopefully lead to discovery of therapeutic targets and novel biomarkers for intestinal cancer.
Supporting Information
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