2002 Fiscal Year Final Research Report Summary
Identification of intracellular target molecules of glyco-genes and functional glycomics for those proteins
| Project/Area Number |
13670121
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General medical chemistry
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| Research Institution | Osaka University |
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Principal Investigator |
MIYOSHI Eiji Osaka University Graduate School of Medicine Div. Biochemistry, Associate Professor, 医学部, 助教授 (20322183)
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| Project Period (FY) |
2001 – 2002
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| Keywords | Hepatocellular carcinoma / Haptoglobin / two-dimensional electrophoresis / GnT-III / GnT-V / Matriptase / Cancer Metastasis / Glycomics |
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| Research Abstract |
I identified intracellular target proteins for GnT-III and GnT-V and analyzed functions of those proteins. When DEN was administered to GnT-III transgenic mice, tumor formation in the liver was dramatically suppressed as compared to control mice. However, a few number of GnT-III transgenic mice treated with DEN had tumors. When serum proteins of those mice were analyzed by two-dimensional ectrophoresis followed by lectin blot, 6 target proteins for GnT-III were identified. One of these proteins was haptoglobin beta- chain. Haptoglobin is a radical scavenger and its function in terms of aberrant glycosylation should be clarified (Free Radical Research 36, 327-833, 2002). I also identified matriptase as a target molecule for GnT-V. Matriptase is one of membrane-anchored serine-protease, which has recently cloned. When GnT-V was transfected into a human gastric cancer cell MKN45, experimental metastasis was markedly promoted. The mechanism was due to induction of matriptase secretion because matriptase bearing beta1-6 GlcNAc branching, a product of GnT-V had a prolongation for degradation. This is the first answer for a question why GnT-V promotes cancer metastasis.
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Research Products
(10 results)
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[Publications] Kitada, T. Miyoshi. E., Noda, K., Higashiyama, S., Ihara, H., Matsuura, N., Hayashi, N., Kawata, S., Matsuzawa, Y., and Taniguchi N.: "Addition of bisecting N-acetylglucosamine residues to: E-cadherin downregulates the tyrosine phosphotylation of β-catenin"J. Biol. Chem.. 276. 475-480 (2001)
Description
「研究成果報告書概要(欧文)」より
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