| Project/Area Number | 13670121 |
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
General medical chemistry
|
|---|
| Research Institution | Osaka University |
|---|
Principal Investigator |
MIYOSHI Eiji Osaka University Graduate School of Medicine Div. Biochemistry, Associate Professor, 医学部, 助教授 (20322183)
|
|---|
| Project Period (FY) |
2001 – 2002
|
| Project Status |
Completed(Fiscal Year 2002)
|
| Budget Amount *help |
¥2,800,000 (Direct Cost : ¥2,800,000)
Fiscal Year 2002 : ¥600,000 (Direct Cost : ¥600,000)
Fiscal Year 2001 : ¥2,200,000 (Direct Cost : ¥2,200,000)
|
|---|
| Keywords | Hepatocellular carcinoma / Haptoglobin / two-dimensional electrophoresis / GnT-III / GnT-V / Matriptase / Cancer Metastasis / Glycomics / がん転移 / ハプトグロビン / 血管新生 / βカテニン |
|---|
| 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.
|
