title: Role of Necl-5 in the pathophysiology of colorectal lesions induced by dimethylhydrazine and/or dextran sodium sulphate.
abstract: Necl-5 is an immunoglobulin-like molecule that was originally identified as a poliovirus receptor. Although Necl-5 expression is often up-regulated in cancer cells, its pathophysiological significance in the development of cancer remains unclear. We investigated the roles of Necl-5 in the development of colitis-associated neoplasia. Necl-5-deficient mice were generated and treated with dimethylhydrazine (DMH) and/or dextran sodium sulphate (DSS) to induce colitis and its associated neoplasias. Colon tissues were examined for histology, Ki-67 expression by immunohistochemistry and K-ras gene mutation. Colon tumours occurred significantly less frequently in heterozygous (Necl-5(+/-)) or homozygous Necl-5-deficient (Necl-5(-/-)) mice than in wild-type (WT) mice with DMH/DSS treatment. Total ulcer index and inflammatory cell infiltration were significantly lower in Necl-5(-/-) mice than in WT mice with DSS alone or DMH/DSS treatment. Colon tumours in both WT and Necl-5(-/-) mice showed high cell proliferation ability but lacked K-ras mutation. The total Ki-67 labelling index in non-neoplastic colon epithelium was significantly higher in WT (45.9 +/- 0.94) than in Necl-5(+/-) (34.3 +/- 1.40) or Necl-5(-/-) (27.7 +/- 1.15) mice with DMH/DSS treatment (p < 0.001). Necl-5 plays a role in the development of colitis-associated cancer by up-regulating colonic mucosal cell proliferation.
authors.affiliation: Department of Surgical and Molecular Pathology, Dokkyo University School of Medicine, Tochigi, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Abe
authors.forename: H
authors.initials: H
authors.lastname: Fukui
authors.forename: S
authors.initials: S
authors.lastname: Fujii
authors.forename: T
authors.initials: T
authors.lastname: Kono
authors.forename: K
authors.initials: K
authors.lastname: Mukawa
authors.forename: N
authors.initials: N
authors.lastname: Yoshitake
authors.forename: A
authors.initials: A
authors.lastname: Sekikawa
authors.forename: K
authors.initials: K
authors.lastname: Ichikawa
authors.forename: S
authors.initials: S
authors.lastname: Tomita
authors.forename: H
authors.initials: H
authors.lastname: Yamagishi
authors.forename: Y
authors.initials: Y
authors.lastname: Imai
authors.forename: M
authors.initials: M
authors.lastname: Shinoda
authors.forename: H
authors.initials: H
authors.lastname: Ishizaki
authors.forename: M
authors.initials: M
authors.lastname: Tanaka-Okamoto
authors.forename: K
authors.initials: K
authors.lastname: Kubota
authors.forename: J
authors.initials: J
authors.lastname: Miyoshi
authors.forename: Y
authors.initials: Y
authors.lastname: Takai
authors.forename: T
authors.initials: T
authors.lastname: Fujimori
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000502:physiology*; D001724:Birth Weight; D015815:Cell Adhesion Molecules / Q000172:deficiency / Q000502:physiology*; D003093:Colitis, Ulcerative / Q000139:chemically induced / Q000150:complications / Q000473:pathology; D003106:Colon / Q000473:pathology; D015179:Colorectal Neoplasms / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D016264:Dextran Sulfate; D004127:Dimethylhydrazines; D004195:Disease Models, Animal; D011905:Genes, ras / Q000235:genetics; D006128:Growth; D007413:Intestinal Mucosa / Q000473:pathology; D019394:Ki-67 Antigen / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation; D009363:Neoplasm Proteins / Q000172:deficiency / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods
chemical_list: D000951:Antigens, Neoplasm; D015815:Cell Adhesion Molecules; D004127:Dimethylhydrazines; D019394:Ki-67 Antigen; D009363:Neoplasm Proteins; C476587:Taa1 protein, mouse; D016264:Dextran Sulfate