2004 Fiscal Year Final Research Report Summary
Proteome analysis in normal liver, chronic hepatitis, liver cirrhosis and hepatocellular carcinoma-For a novel diagnosis, treatment and protection of hepatocellular carcinoma
| Project/Area Number |
15590654
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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 |
Gastroenterology
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| Research Institution | Kagawa University |
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Principal Investigator |
MASAKI Tsutomu Kagawa University of Medicine, Third Department of Internal Medicine, Research Associate, 医学部, 助手 (30335848)
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| Co-Investigator(Kenkyū-buntansha) |
KURIYAMA Shigeki Kagawa University, Third Department of Internal Medicine, Professor, 医学部, 教授 (50244710)
WATANABE Seishiro Kagawa University, Third Department of Internal Medicine, Associate Professor, 医学部, 助教授 (00158635)
KUROKOHCHI Kazutaka Kagawa University, Third Department of Internal Medicine, Research Assistant, 医学部, 助手 (10294753)
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| Project Period (FY) |
2003 – 2004
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| Keywords | hepatocllular carcinoma / cell cycle / Cdk / Cdk inhibitor / p18^<INK4C> |
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| Research Abstract |
Cyclins, cyclin-dependent kinases (Cdks), and Cdk inhibitors (CdkIs) are frequently altered in human cancer. p 18^<INK4C>, a member of the INK4 family among CdkIs, is a potential tumor suppressor gene product. However, the expression of p 18^<INK4C> in hepatocellular carcinoma (HCC) remains unknown. The aim of this study was to examine the expression of p18^<INK4C> in various liver diseases including HCC and to assess its clinical significance in HCC. To that end, we examined the expression of p 18^<INK4C> by immunohistochemistry in various liver diseases including 51 HCCs, and also studied the relationship among p 18^<INK4C> expression, the phosphorylation of retinoblastoma protein (pRb), and the activity level of Cdk4 and Cdk6. Immunohistochemical analysis revealed the frequent loss of p18^<INK4C> expression in HCC, especially in poorly differentiated HCC. The loss of p18^<INK4C> expression was shown to be associated with a poor prognosis as compared with that associated with p18^<INK4C>-positivity. Further, the kinas activity of Cdk4 was found to be higher in p18^<INK4C>-negative HCCs than in p 18^<INK4C>-positive HCCs. However, the level of Cdk6 activity was similar in the two groups of HCCs. In p18^<INK4C>-positive HCCs, p18^<INK4C> dominantly interacted with Cdk4 rather than with Cdk6. pRb phosphorylated at Ser 780 was detected more frequently in p18^<INK4C>-negative than in p 18^<INK4C>-positive HCCs. These data suggest that the loss of p18^<INK4C> expression may play a role in the differentiation and development of HCC through the upregulation of Cdk4 activity.
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