| Project/Area Number |
16591327
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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 |
Digestive surgery
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| Research Institution | KYUSHU UNIVERCITY |
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Principal Investigator |
TAKETOMI Akinobu Kyushu University Hospital, Research Associate, 大学病院, 助手 (70363364)
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| Co-Investigator(Kenkyū-buntansha) |
SAKANE Fumio Sapporo Medical College, Dept. of Biochemistry, Associate Profeffor, 医学部, 助教授 (10183815)
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| Project Period (FY) |
2004 – 2005
|
| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2005: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2004: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Keywords | diacylglycerol kinase / hepatocellular carcinoma / RT-PCR |
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| Research Abstract |
Diacylglycerol kinases (DGKs), which catalyze phosphorylation of diacylglycerol (DAG) to phophatidic acid (PA), play an important role in the signal transduction downstream of phospholipid turnover. To characterize its role of neoplastic transformation, mouse embryonic fibroblasts derived from dgkd^<+/+> or dgkd^<+/-> were used. Dgkd^<+/-> cells were profoundly growth-inhibited versus dgkd^<+/+> cells. Dgkd^<+/-> cells showed a 50% decrease of inhibition of BrdU incorporation compared with dgkd^<+/+> cells. Foci formation of dgkd^<+/-> cells induced by H-Ras and SV40 T antigen was significantly suppressed when compared with that of dgkd^<+/+> cells. A neutralizing antibody to TGFα drastically reduced the number of foci of dgkd^<+/+> cells to the same level as that of dgkd^<+/-> cells. Semi-quantitative RT-PCR showed that DGKδ expression was upregulated in human hepatocellular carcinoma (HCC), in which a soluble form of TGFα was detected in large quantities in blood or urine, compared in non-cancerous liver tissues. Immunohistochemical study revealed that strong DGKδ-immunoreactivity was present at the leading edge of HCC, such as the site near portal vein or under the capsule of the tumor, in which high expression of TACE and TGFα was also detected.
These observations provide a novel molecular mechanism of transformation and tumor progression via DGKδ action and a suitable therapeutic target in HCC.
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