| Project/Area Number |
15590620
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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 | The University of Tokyo |
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Principal Investigator |
TERATANI Takuma The University of Tokyo, Faculty of Medicine, Assistant, 医学部附属病院, 助手 (30359616)
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| Co-Investigator(Kenkyū-buntansha) |
YOSHIDA Haruhiko The University of Tokyo, Faculty of Medicine, Lecturer, 医学部附属病院, 講師 (60240305)
KATO Naoya The University of Tokyo, Faculty of Medicine, Assistant, 医学部附属病院, 助手 (90313220)
KAWAKAMI Takayuki The University of Tokyo, Faculty of Medicine, Medical Staff, 医学部附属病院, 医員 (60376457)
OTSUKA Motoyuki The University of Tokyo, Faculty of Medicine, Medical Staff, 医学部附属病院, 医員
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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: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2003: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | vitaminK / hepatocellular carcinoma / DCP |
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| Research Abstract |
Hepatocellular carcinoma (HCC) is a common human malignancy. Its high mortality rate is mainly a result of high intrahepatic recurrence and portal venous invasion. We previously reported that the development of portal venous invasion is related to levels of des-gamma-carboxy prothrombin (DCP), a serum protein that increases at a notably higher rate in patients with HCC. Because DCP is produced by a vitamin K shortage, we examined the biological effects of extrinsic supplementation of vitamin K2 in HCC cells in vitro. Consequently, vitamin K2 inhibits the growth and invasion of HCC cells through the activation of protein kinase A (PKA), which modulates the activities of several transcriptional factors, independent of suppression of DCP. In addition, vitamin K-binding proteins were characterized by pull-down experiment using a chemically synthesized biotynylated vitamin K followed by mass spectrometric identification of the pull-downed components. The results showed that Vitamin K2 binds 17β hydroxysteroid dehydrogenase 4 and decreases the intracellular estradiol : estrone ratio. These results suggest a possible role for vitamin K in modulating cell growth and estrogen function, and vitamin K2 may be a promising drug for hepatocellular carcinoma.
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