| Project/Area Number |
17390119
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Experimental pathology
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| Research Institution | Miyagi Cancer Center Research Institute |
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Principal Investigator |
MIYAGI Taeko Miyagi Cancer Center Research Institute, Division of Biochemistry, Institute Head, 生化学部, 所長兼部長 (50006110)
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| Co-Investigator(Kenkyū-buntansha) |
SHIOZAKI Kazuhiro Miyagi Cancer Center Research Institute, Division of Biochemistry, Visiting scientist, 生化学部, 共同研究員 (70390896)
HATA Keiko Miyagi Cancer Center Research Institute, Division of Biochemistry, Visiting scientist, 生化学部, 共同研究員 (60390895)
TATENO Hiroo Miyagi Cancer Center Research Institute, Division of Pathology, Department director, 病理学部, 部長 (70004744)
SATO Ikuro Miyagi Cancer Center Research Institute, Division of Pathology, General Research worker, 病理学部, 総括研究員 (50225918)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥7,800,000 (Direct Cost: ¥7,800,000)
Fiscal Year 2006: ¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2005: ¥4,100,000 (Direct Cost: ¥4,100,000)
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| Keywords | cancer / enzyme / sugar chain / sialidase / gene / tumor-related antigen / sialic acid / cell adhesion |
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| Research Abstract |
Sialidase catalyzes the removal of sialic acid residues from glycoproteins and glycolipids, and consistently changes in the expression during cell differentiation, cell growth, and malignant transformation. Of four types of mammalian sialidases so far cloned, here we characterized the recently identified NEU4 and found its altered expression and influence on the malignant phenotype in colon cancers. NEU4 possessed short and long isoforms and the latter to be located in mitochondria, and unlike other sialidases, NEU4 was able to hydrolyze significantly mucins including sialylLe^x and sialylLe^a structures. Human colon mucosa was relatively rich in NEU4, but hardly contained the long form. In clear contrast to the NEU3 case, the level of mRNA was markedly decreased in colon cancers. In cultured human colon cancer cells, the enzyme was up-regulated in apoptosis induced by either the death ligand TRAIL or serum-depletion, and transfection of NEU4 resulted in acceleration of apoptosis and in decreased invasion and motility. The siRNA-mediated NEU4 targeting, on the other hand, caused the opposite. Lectin blot analyses revealed that desialylated forms of nearly 100 kDa glycoproteins were prominently increased with peanut agglutinin (PNA) in NEU4 transfectants, whereas only slight changes in glycolipids were detected. These results suggest that NEU4 plays important roles for maintenance of normal mucosa mostly through desialylation of glycoproteins and that down-regulation may contribute to malignant properties of colon cancers.
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