title: AP1B plays an important role in intestinal tumorigenesis with the truncating mutation of an APC gene.
abstract: 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 APC(Min/+)  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.
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan.
authors.forename: Mitsuko
authors.initials: M
authors.lastname: Mimura
authors.forename: Atsuhiro
authors.initials: A
authors.lastname: Masuda
authors.forename: Shin
authors.initials: S
authors.lastname: Nishiumi
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Kawakami
authors.forename: Yoshimi
authors.initials: Y
authors.lastname: Fujishima
authors.forename: Tomoo
authors.initials: T
authors.lastname: Yoshie
authors.forename: Shigeto
authors.initials: S
authors.lastname: Mizuno
authors.forename: Ikuya
authors.initials: I
authors.lastname: Miki
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ohno
authors.forename: Koji
authors.initials: K
authors.lastname: Hase
authors.forename: Toshinari
authors.initials: T
authors.lastname: Minamoto
authors.forename: Takeshi
authors.initials: T
authors.lastname: Azuma
authors.forename: Masaru
authors.initials: M
authors.lastname: Yoshida
mesh_terms: D033961:Adaptor Protein Complex 1 / Q000502:physiology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D002460:Cell Line; D045744:Cell Line, Tumor; D016764:Cell Polarity / Q000235:genetics*; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000235:genetics; D015536:Down-Regulation; D004847:Epithelial Cells; D005260:Female; D017491:Genes, APC; D006801:Humans; D007414:Intestinal Neoplasms / Q000235:genetics*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation; D013552:Swine; D051176:beta Catenin / Q000378:metabolism
chemical_list: D033961:Adaptor Protein Complex 1; D051176:beta Catenin