1998 Fiscal Year Annual Research Report

ウイルス性肝発がんの分子要因

Research Project

Project/Area Number	09253102
Research Category	Grant-in-Aid for Scientific Research on Priority Areas (A)
Research Institution	Kyoto University
Principal Investigator	下遠野邦忠京都大学, ウイルス研究所, 教授 (10000259)
Co-Investigator(Kenkyū-buntansha)	林紀夫大阪大学, 医学部, 教授 (00144478) 小原道法東京都臨床医学総合研究所, 放射線研究部, 室長 (10250218) 金子周一金沢大学, 医学部, 助教授 (60185923) 村上清史金沢大学, がん研究所, 教授 (90019878) 小池克郎癌研究会癌研究所, 遺伝子研究施設部, 部長 (30085625)
Keywords	B型肝炎ウイルス / C型肝炎ウイルス / 染色体不安定性 / 細胞障害性T細胞 / X蛋白質 / がん抑制遺伝子 / p53 / アポトーシス
Research Abstract	ウイルス肝発がんの分子機構を感染細胞のゲノムの不安定性をウイルス遺伝子あるいはウイルスゲノム自身が惹起する可能性、ウイルス感染により引き起される肝炎が免疫機構により惹起される肝炎と比較したときに質的あるいは量的な違いが生じるか否かを分子レベルで解析することを目的として研究し、以下の成績を得た。HBVによる感染細胞の増殖制御に関して細胞質に局在するX蛋白質がミトコンドリア上に局在すること、がん抑制遺伝子p53と相互作用してp53の細胞内局在を変化させることを明かにした。一方、HBVゲノムの組み換えに関与する領域に結合する細胞性蛋白質を分子クローンした。HBVX蛋白質が転写補助因子としての機能を持つことを明かにした。HCV蛋白質が細胞の蛋白質キナーゼと会合し、キナーゼ活性を抑制することを示唆する知見を得た。その結果、HCV感染細胞において細胞増殖の一過性の持続が予測される。即ち、感染細胞においてはアポトーシスを抑制する可能性を明かにした。これらの成果はウイルス感染により細胞染色体の不安定化が助長される可能性を示唆するものである。 HCV特異的細胞障害性T細胞(CTL)の誘発にB7-1遺伝子導入が有用であることを示した。また、樹状細胞を抗原提示細胞として用いることにより高い活性を示すHCV特異的CTLの誘導が可能であることを示した。

Research Products
(28 results)

All Other

All Publications (28 results)

[Publications] Ibe M.: "Identification and characterization of a cytotoxic T cell epitope of hepatitis C virus presented by HLA-Bα3501 in acute hepatitis." J.gen Virol.79. 1735-1744 (1998)
[Publications] Inoue H.: "Expression of a hepatitis C virus NS3 protease-NS4A fusion protein in Escherichia coli." Biochem.Biophys.Res.Commun.245. 478-482 (1998)
[Publications] Kakiuchi N: "Non-peptide inhibitors of HCV serine proteinase." FEBS Letters. 421. 217-220 (1998)
[Publications] Koike K.: "Hepatitis B virus DNA is frequently found in the liver biopsy samples from hepatitis C virus-infected chronic hepatitis patients." J.Med.Virol.54. 249-255 (1998)
[Publications] Shimazu T.: "Post-transcriptional control of the level of mRNA by hepatitis B virus X gene in the transient expression system using human hepatic cells." Genes to Cells. 3. 477-484 (1998)
[Publications] Dorjsuren D.: "RMP, a novel RNA polymerase II subunit 5-interacting protein, counteracts transactivation by hepatitis B virus X protein." Mol.Cell.Biol.18. 7546-7555 (1998)
[Publications] Lin Y.: "The HBV X protein is a co-activator of activated transcription that modulates the transcription machinery and distal binding activators." J.Biol.Chem.273. 27097-27103 (1998)
[Publications] Yamashita T.: "RNA-dependent RNA polymerase activity of the soluble recombinant Hepatitis C Virus NS5B protein truncated at the C-terminal region." J.Biol.Chem.273. 15479-15486 (1998)
[Publications] Wakita T.: "Efficient conditional transgene expression in hepatitis C virus cDNA transgenic mice mediated by the Cre/IoxP system." J.Biol.Chem.273. 9001-9006 (1998)
[Publications] Oh Y.L.: "Determination of functional domains in polypyrimidin-tract-binding protein." Biochem.J.331. 169-175 (1998)
[Publications] Yasui K.: "The native form and maturation process of hepatitis C virus core protein." J.Virology. 72. 6048-6055 (1998)
[Publications] Urabe T.: "Clinical pilot study of intrahepatic arterial chemotherapy with Methotrexate, 5-Fluorouracil, Cisplatin and subcutaneous Interferon Alpha-2b for patients with locally advanced hepatocellular carcinoma." Oncology. 55. 39-47 (1998)
[Publications] Mizukoshi E.: "Expression of interferon α/β receptor in the liver of chronic hepatitis C patients." J.Med.Virol.56. 217-223 (1998)
[Publications] Terasaki S.: "Histologic feature predicting malignant transformation of nonmalignant hepatocellular nodules: a prosptective study." Gastroenterology. 115. 1216-1222 (1998)
[Publications] Kuzushita N.: "Influence of HLA haplotypes on the clinical courses of individuals infected with hepatitis C virus." Hepatology.27. 240-244 (1998)
[Publications] Kasahara A.: "Risk factors for hepatocellular carcinoma and its incidence after interferon treatment in patients with chronic hepatitis C." Hepatology.27. 1394-1402 (1998)
[Publications] Ito Y.: "Activation of mitogen-activated protein kinase/extracellular signal-regulated kinase in human hepatocellular carcinoma." Hepatology.27. 951-958 (1998)
[Publications] Takehara T.: "Delayed Fas-mediated hepatocyte apoptosis during liver regeneration in mice: Hepatoprotective role of TNF α." Hepatology.27. 1643-1651 (1998)
[Publications] Kanto T.: "Cross-linking of Fc γ-receptor on monocytes inhibits hepatitis C virus-specific cytotoxic T lymphocyte induction in vitro." Immunology.94. 461-468 (1998)
[Publications] Noda K.: "Gene expression of α 1-6 fucosyltransferase in human hepatoma tissues: A pos sible implication for increased fucosylation of α-fetoptotein." Hepatology.28. 944-952 (1998)
[Publications] Tanaka H.: "Hepatitis C virus 1b(II) infection and development of chronic hepatitis, liver cirrhosis and hepatocellular carcinoma: a case-control study in Japan." J.Epidemiol.8. 244-249 (1998)
[Publications] Oshita M.: "GBV-C/HGV infection in chronic hepatitis C patients: Its effect on clinical features and interferon therapy." J.Med.Virol.55. 98-102 (1998)
[Publications] Wada S.: "Involvement of growth factor receptor-bound protein-2 in rat hepatocyte growth." J.Gastrol.Hepatol.13. 635-642 (1998)
[Publications] Iio S.: "Serum levels of soluble Fas antigen in chronic hepatitis C patients." J.Hepatol.29. 517-523 (1998)
[Publications] Noda K.: "High expression of α 1-6 fucosyltransferase during rat hepatocarcinogenesis." Int.J.Cancer.75. 444-450 (1998)
[Publications] Yamamoto T.: "Hepatocellular carcinomas infected with the novel TT DNA virus lack viral integration." Biochemical Biophysical Research Communications.251. 339-343 (1998)
[Publications] Pugh JC.: "Aberrant expression of a cytokeratin in a subset of hepatocytes during chronic WHV infection." Virology.249. 68-79 (1998)
[Publications] Sakai A.: "Floating density of hepatitis C virus paricles and response to interferon treatment." J.Med.Virol.55. 12-17 (1998)

1998 Fiscal Year Annual Research Report

ウイルス性肝発がんの分子要因

Principal Investigator

下遠野 邦忠 京都大学, ウイルス研究所, 教授 (10000259)

Research Products

[Publications] Ibe M.: "Identification and characterization of a cytotoxic T cell epitope of hepatitis C virus presented by HLA-Bα3501 in acute hepatitis." J.gen Virol.79. 1735-1744 (1998)

[Publications] Inoue H.: "Expression of a hepatitis C virus NS3 protease-NS4A fusion protein in Escherichia coli." Biochem.Biophys.Res.Commun.245. 478-482 (1998)

[Publications] Kakiuchi N: "Non-peptide inhibitors of HCV serine proteinase." FEBS Letters. 421. 217-220 (1998)

[Publications] Koike K.: "Hepatitis B virus DNA is frequently found in the liver biopsy samples from hepatitis C virus-infected chronic hepatitis patients." J.Med.Virol.54. 249-255 (1998)

[Publications] Shimazu T.: "Post-transcriptional control of the level of mRNA by hepatitis B virus X gene in the transient expression system using human hepatic cells." Genes to Cells. 3. 477-484 (1998)

[Publications] Dorjsuren D.: "RMP, a novel RNA polymerase II subunit 5-interacting protein, counteracts transactivation by hepatitis B virus X protein." Mol.Cell.Biol.18. 7546-7555 (1998)

[Publications] Lin Y.: "The HBV X protein is a co-activator of activated transcription that modulates the transcription machinery and distal binding activators." J.Biol.Chem.273. 27097-27103 (1998)

[Publications] Yamashita T.: "RNA-dependent RNA polymerase activity of the soluble recombinant Hepatitis C Virus NS5B protein truncated at the C-terminal region." J.Biol.Chem.273. 15479-15486 (1998)

[Publications] Wakita T.: "Efficient conditional transgene expression in hepatitis C virus cDNA transgenic mice mediated by the Cre/IoxP system." J.Biol.Chem.273. 9001-9006 (1998)

[Publications] Oh Y.L.: "Determination of functional domains in polypyrimidin-tract-binding protein." Biochem.J.331. 169-175 (1998)

[Publications] Yasui K.: "The native form and maturation process of hepatitis C virus core protein." J.Virology. 72. 6048-6055 (1998)

[Publications] Urabe T.: "Clinical pilot study of intrahepatic arterial chemotherapy with Methotrexate, 5-Fluorouracil, Cisplatin and subcutaneous Interferon Alpha-2b for patients with locally advanced hepatocellular carcinoma." Oncology. 55. 39-47 (1998)

[Publications] Mizukoshi E.: "Expression of interferon α/β receptor in the liver of chronic hepatitis C patients." J.Med.Virol.56. 217-223 (1998)

[Publications] Terasaki S.: "Histologic feature predicting malignant transformation of nonmalignant hepatocellular nodules: a prosptective study." Gastroenterology. 115. 1216-1222 (1998)

[Publications] Kuzushita N.: "Influence of HLA haplotypes on the clinical courses of individuals infected with hepatitis C virus." Hepatology.27. 240-244 (1998)

[Publications] Kasahara A.: "Risk factors for hepatocellular carcinoma and its incidence after interferon treatment in patients with chronic hepatitis C." Hepatology.27. 1394-1402 (1998)

[Publications] Ito Y.: "Activation of mitogen-activated protein kinase/extracellular signal-regulated kinase in human hepatocellular carcinoma." Hepatology.27. 951-958 (1998)

[Publications] Takehara T.: "Delayed Fas-mediated hepatocyte apoptosis during liver regeneration in mice: Hepatoprotective role of TNF α." Hepatology.27. 1643-1651 (1998)

[Publications] Kanto T.: "Cross-linking of Fc γ-receptor on monocytes inhibits hepatitis C virus-specific cytotoxic T lymphocyte induction in vitro." Immunology.94. 461-468 (1998)

[Publications] Noda K.: "Gene expression of α 1-6 fucosyltransferase in human hepatoma tissues: A pos sible implication for increased fucosylation of α-fetoptotein." Hepatology.28. 944-952 (1998)

[Publications] Tanaka H.: "Hepatitis C virus 1b(II) infection and development of chronic hepatitis, liver cirrhosis and hepatocellular carcinoma: a case-control study in Japan." J.Epidemiol.8. 244-249 (1998)

[Publications] Oshita M.: "GBV-C/HGV infection in chronic hepatitis C patients: Its effect on clinical features and interferon therapy." J.Med.Virol.55. 98-102 (1998)

[Publications] Wada S.: "Involvement of growth factor receptor-bound protein-2 in rat hepatocyte growth." J.Gastrol.Hepatol.13. 635-642 (1998)

[Publications] Iio S.: "Serum levels of soluble Fas antigen in chronic hepatitis C patients." J.Hepatol.29. 517-523 (1998)

[Publications] Noda K.: "High expression of α 1-6 fucosyltransferase during rat hepatocarcinogenesis." Int.J.Cancer.75. 444-450 (1998)

[Publications] Yamamoto T.: "Hepatocellular carcinomas infected with the novel TT DNA virus lack viral integration." Biochemical Biophysical Research Communications.251. 339-343 (1998)

[Publications] Pugh JC.: "Aberrant expression of a cytokeratin in a subset of hepatocytes during chronic WHV infection." Virology.249. 68-79 (1998)

[Publications] Sakai A.: "Floating density of hepatitis C virus paricles and response to interferon treatment." J.Med.Virol.55. 12-17 (1998)

下遠野邦忠京都大学, ウイルス研究所, 教授 (10000259)