Identification of genes associated with poor prognosis
| Project/Area Number |
15590058
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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 |
Biological pharmacy
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| Research Institution | Hamamatsu University School of Medicine |
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Principal Investigator |
KITAGAWA Kyoko Hamamatsu University School of Medicine, Assistant Professor, 医学部, 助手 (20299605)
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| Co-Investigator(Kenkyū-buntansha) |
KITAGAWA Masatoshi Hamamatsu University School of Medicine, Professor, 医学部, 教授 (50294971)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2004: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2003: ¥2,400,000 (Direct Cost: ¥2,400,000)
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| Keywords | ubiquitin / p27Kip1 / colorectal carcinoma / cell cycle / Skp2 / intracellular signaling / 癌抑制遺伝子産物 |
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| Research Abstract |
A cyclin-dependent kinase (CDK) inhibitor p27^<Kip1> acts as a critical negative regulator of the cell. Degradation of p27^<Kip1> activates G1 cyclin-CDK complexes to promote the cell cycle progression from the G1 to S phase. Many clinical studies have indicated that reduced expression of p27^<Kip1> is found in many types of human cancers, including breast and colorectal carcinomas and highly associated with their high aggressiveness and poor prognosis. The decreased level of p27^<Kip1> expression in human cancers is due to enhanced degradation of p27^<Kip1> via ubiquitin-proteasome pathway. It is demonstrated that degradation of p27^<Kip1> is promoted by SCF^<Skp2>, an SCF-type ubiquitin ligase, which ubiquitinates p27^<Kip1> to target ubiquitin-dependent degradation through the 26S-proteasome However, it is unknown the cause of high aggressiveness or poor prognosis in the tumors with low p27^<Kip1>-expression. To solve the mater, we tried to identify the genes which expressions were affected by the reduction of p27^<Kip1>-expression. In the present study, we performed targeted disruption of human p27^<Kip1> gene in HCT116, human colorectal carcinoma cell lines in order to establish a model cell line with low expression of p27^<Kip1>. We found a gene, PPAG4, which was induced by the reduction of p27^<Kip1>-expression.
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Report
(3 results)
Research Products
(44 results)
