Role of Necl-5 in the pathophysiology of colorectal lesions induced by dimethylhydrazine and/or dextran sodium sulphate.
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.
Abe
A
A
Department of Surgical and Molecular Pathology, Dokkyo University School of Medicine, Tochigi, Japan.
Fukui
H
H
Fujii
S
S
Kono
T
T
Mukawa
K
K
Yoshitake
N
N
Sekikawa
A
A
Ichikawa
K
K
Tomita
S
S
Yamagishi
H
H
Imai
Y
Y
Shinoda
M
M
Ishizaki
H
H
Tanaka-Okamoto
M
M
Kubota
K
K
Miyoshi
J
J
Takai
Y
Y
Fujimori
T
T
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
D000951:Antigens, Neoplasm; D015815:Cell Adhesion Molecules; D004127:Dimethylhydrazines; D019394:Ki-67 Antigen; D009363:Neoplasm Proteins; C476587:Taa1 protein, mouse; D016264:Dextran Sulfate