2004 Fiscal Year Final Research Report Summary
Study on the mechanism of hepatocarcinogenesis in hepatitis C viral infection
| Project/Area Number |
13214018
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research on Priority Areas
|
| Allocation Type | Single-year Grants |
|---|
| Review Section |
Biological Sciences
|
|---|
| Research Institution | The University of Tokyo |
|---|
Principal Investigator |
KOIKE Kazuhiko University of Tokyo, Graduate School of Medicile, Proissor, 医学部附属病院, 教授 (80240703)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
新谷 良澄 東京大学, 医学部附属病院, 助手 (80261965)
MIYOSHI Hideyuki University of Tokyo, Faculty of Medicine, Research Investigator, 医学部附属病院, 医員
MORIYA Kyoji University of Tokyo, Faculty of Medicine, Associate Professor, 医学部附属病院, 講師 (00272550)
KOIKE Kazuhiko University of Tokyo, Faculty of Medicine, Research Associate (80240703)
|
|---|
| Project Period (FY) |
2001 – 2004
|
| Keywords | hepatitis C virus / hepatocarcinogenesis / transgenic mouse / core protein / oxidative stress / intracellular signal transduction / retinoid X receptor / insulin resistance |
|---|
| Research Abstract |
Despite numerous lines of epidemiological evidence connecting hepatitis C virus (HCV) infection and the development of hepatocellular carcinoma (HCC), it remains controversial whether HCV itself plays a direct role or an indirect role in the pathogenesis of HCC. Through the use of transgenic mice, it has become evident that the core protein of HCV has an oncogenic potential. HCV is directly involved in hepatocarcinogenesis, albeit other factors such as inflammation and environmental factors may also play a role. The direct involvement of HCV in hepatocarcinogenesis would be achieved via two pathways. In one pathway, the core protein acts on the function of mitochondria, leading to the overproduction of oxidative stress, which yields genetic aberrations in cell-growth-related genes. The other pathway involves the modulations of cellular gene expressions and intracellular signal transductions, such as mitogen-activated protein kinases (MAPKs) pathway, which results in the activation of transcription factors and cell cycle machineries. The combination of these alterations would provoke the development of HCC in HCV infection. This would be a mechanism for HCC development in HCV infection that is distinct from those for other cancers. The presence of the HCV core protein, to which an oncogenic potential is ascribed, may allow some of the multiple steps to be bypassed in hepatocarcinogenesis. Therefore, unlike in other cancers, HCV infection can elicit HCC in the absence of a complete set of genetic aberrations. Such a scenario, "non-Vogelstein-type" carcinogenesis, would explain the unusually high incidence and multicentric nature of HCC development in HCV infection.
|
-
-
[Journal Article] Hepatitis C Virus Core Protein Exerts an Inhibitory Effect on Suppressor of Cytokine Signaling (SOCS)-1 Gene Expression.2005
Author(s)
Miyoshi H, Fujie H, Shintani Y, Tsutsumi T, Shinzawa S, Makuuchi M, Kokudo N, Matsuura Y, Suzuki T, Miyamura T, Moriya K, Koike K.
-
Journal Title
Description
「研究成果報告書概要(欧文)」より
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
[Journal Article] Increase in the concentration of carbon 18 monounsaturated fatty acids in the liver with hepatitis C : analysis in transgenic mice and humans.2001
Author(s)
Moriya K, Todoroki T, Tsutsumi T, Fujie H, Shintani Y, Miyoshi H, Ishibashi K, Takayama T, Makuuchi M, Watanabe K, Miyamura T, Kimura S, Koike K.
-
Journal Title
Biophys Biochem Res Commun 281
Pages: 1207-1212
Description
「研究成果報告書概要(欧文)」より
-
-
-
[Journal Article] Oxidative stress in the absence of inflammation in a mouse model for hepatitis C virus-associated hepatocellular carcinogenesis.2001
Author(s)
Moriya K, Nakagawa K, Santa T, Shintani Y, Fujie H, Miyoshi H, Tsutsumi T, Miyazawa T, Ishibashi K, Horie T, Imai K, Miyamura T, Kimura S, Koike K.
-
Journal Title
Cancer Res 61
Pages: 4365-4370
Description
「研究成果報告書概要(欧文)」より
-
-
[Journal Article] Virological analysis of non-B, non-C hepatocellular carcinoma in Japan : frequent involvement of hepatitis B virus2000
Author(s)
Yotsuyanagi H, Shintani Y, Moriya K, Fujie H, Tsutsumi T, Kato T, Nishioka K, Takayama T, Makuuchi M, Iino S, Kimura S, Koike K.
-
Journal Title
J Infect Dis 181
Pages: 1920-1928
Description
「研究成果報告書概要(欧文)」より
