1999 Fiscal Year Annual Research Report

肝細胞と肝癌細胞におけるGenomics

Research Project

Project/Area Number	11307010
Research Category	Grant-in-Aid for Scientific Research (A)
Research Institution	Kanazawa University
Principal Investigator	小林健一金沢大学, 医学部, 教授 (70019933)
Co-Investigator(Kenkyū-buntansha)	中本安成金沢大学, 医学部・附属病院, 助手 (40293352) 本多政夫金沢大学, 医学部・附属病院, 助手 (00272980) 金子周一金沢大学, 医学部, 助教授 (60185923)
Keywords	SAGE / DNA microarray / 肝細胞癌 / Genomics
Research Abstract	肝細胞と肝細胞癌におけるGenomicsを明らかにするため、以下の研究を行った。 1)正常肝組織における発現遺伝子の種類、発現頻度のSAGE法による解析正常肝組織より抽出した30982個のmRNA全ての遺伝子の塩基配列を解析しcomputer searchにて検討したところ、8596個は単独の遺伝子であった。発現頻度に関する検討では、正常肝細胞で最も多く発現されている遺伝子は血漿タンパク質で全転写産物の21.8%を占めていた。次いで細胞質タンパク(8.6%)、諸酵素(4.8%)、蛋白分解酵素阻害蛋白(1.7%)、補体(1.1%)、凝固因子(0.75%)であった。13.9%の遺伝子はこれまでに報告されていない未知の遺伝子であった。これらの正常肝細胞における発現遺伝子種と頻度に関する知識は、肝癌細胞における遺伝子発現を検討する上での基礎的資料であると同時に、DNA microarrayer作成に用いる遺伝子群選択の重要な資料となる。 2)DNA microarray法による肝細胞癌、癌部・非癌部の遺伝子発現比の検討 936既知遺伝子でDNA microarrayerを作成し、臨床検体を用いた解析条件の設定を行った。この条件下で肝細胞癌10症例個々の癌部・非癌部より抽出したmRNAの発現比を検討した。5例以上の症例に共通して、非癌部に比して癌部で発現量が2倍以上亢進している遺伝子が14種同定された。反対に0.5倍以下に発現量が低下している遺伝子が9種同定された。これらの遺伝子は肝細胞癌を特徴付ける遺伝子と考えられる。

Research Products
(14 results)

All Other

All Publications (14 results)

[Publications] Rieko Saeki: "Intratumoral genomic heterogeneity in human hepatocellular carcinoma detected by restriction landmark genomic scanning"Journal of Hepatology. (in press).
[Publications] Taro Yamashita: "Comprehensive gene expression profile of a normal human liver"Biochemical and Biophysical Research Communications. (in press).
[Publications] Masao Honda: "Cell cycle regulation of hepatitis C virus IRES-directed translation"Gastroenterology. 118. 152-162 (2000)
[Publications] Aki Takeuchi: "Interferon-alpha modulates resistance to cisplatin in three human hepatoma cell lines"Journal of Gastroenterology. 34. 351-358 (1999)
[Publications] Katsuro Koike: "Survey of hepatitis B virus co-infection in hepatitis C virus infected patients suffering from chronic hepatitis and hepatocellular carcinoma in Japan"Japanese Journal of Cancer Research. 90. 1270-1272 (1999)
[Publications] Miyoko Natsume: "Attenuated liver fibrosis and depressed serum albumin levels in carbon tetrachloride-treated IL-6-deficient mice"Journal of Leukocyte Biology. 66. 601-608 (1999)
[Publications] Eishiro Mizukoshi: "Serum level of soluble interferon alpha/beta receptor as an inhibitory factor of IFN in the patients with chronic hepatitis C"Hepatology. 30. 1325-1331 (1999)
[Publications] Akito Sakai: "Quasispecies of hepatitis C virus in serum and in three different parts of the liver of patients with chronic hepatitis"Hepatology. 30. 556-561 (1999)
[Publications] Yasunari Nakamoto: "Inhibition of peripheral blood lymphocyte apoptosis by soluble Fas ligand in patients with hepatocellular carcinoma"Oncology Report. 6. 733-739 (1999)
[Publications] Eishiro Mizukoshi: "Up-regulation of Type I interferon receptor by interferon-gamma."Journal of Interferon and Cytokine Research. 19. 1019-1023 (1999)
[Publications] Takayoshi Koura: "Investigation of albumin-synthesizing ability in rat cirrhotic liver-directed hepatocytes using primary hepatocyte culture"Journal of Hepatology. 31. 293-299 (1999)
[Publications] Hideko Ohono: "Human hepatitis B virus X protein augments the DNA binding of NF-IL6 through its basic-leucine zipper domain"Journal of Medical Virology. 58. 11-18 (1999)
[Publications] Shuichi Kaneko: "In Nagy Habib (eds): "Methods in Molecular Medicine""Gene therapy vectors harvoring AFP regulatory sequences: preparation of an adenoviral vector (in press).
[Publications] Shuichi Kaneko: "In Sudhir Srivastava (eds): "Molecular Pathology of Early Cancer""Liver Cancer. 9 (1999)

1999 Fiscal Year Annual Research Report

肝細胞と肝癌細胞におけるGenomics

Principal Investigator

小林 健一 金沢大学, 医学部, 教授 (70019933)

Research Products

[Publications] Rieko Saeki: "Intratumoral genomic heterogeneity in human hepatocellular carcinoma detected by restriction landmark genomic scanning"Journal of Hepatology. (in press).

[Publications] Taro Yamashita: "Comprehensive gene expression profile of a normal human liver"Biochemical and Biophysical Research Communications. (in press).

[Publications] Masao Honda: "Cell cycle regulation of hepatitis C virus IRES-directed translation"Gastroenterology. 118. 152-162 (2000)

[Publications] Aki Takeuchi: "Interferon-alpha modulates resistance to cisplatin in three human hepatoma cell lines"Journal of Gastroenterology. 34. 351-358 (1999)

[Publications] Katsuro Koike: "Survey of hepatitis B virus co-infection in hepatitis C virus infected patients suffering from chronic hepatitis and hepatocellular carcinoma in Japan"Japanese Journal of Cancer Research. 90. 1270-1272 (1999)

[Publications] Miyoko Natsume: "Attenuated liver fibrosis and depressed serum albumin levels in carbon tetrachloride-treated IL-6-deficient mice"Journal of Leukocyte Biology. 66. 601-608 (1999)

[Publications] Eishiro Mizukoshi: "Serum level of soluble interferon alpha/beta receptor as an inhibitory factor of IFN in the patients with chronic hepatitis C"Hepatology. 30. 1325-1331 (1999)

[Publications] Akito Sakai: "Quasispecies of hepatitis C virus in serum and in three different parts of the liver of patients with chronic hepatitis"Hepatology. 30. 556-561 (1999)

[Publications] Yasunari Nakamoto: "Inhibition of peripheral blood lymphocyte apoptosis by soluble Fas ligand in patients with hepatocellular carcinoma"Oncology Report. 6. 733-739 (1999)

[Publications] Eishiro Mizukoshi: "Up-regulation of Type I interferon receptor by interferon-gamma."Journal of Interferon and Cytokine Research. 19. 1019-1023 (1999)

[Publications] Takayoshi Koura: "Investigation of albumin-synthesizing ability in rat cirrhotic liver-directed hepatocytes using primary hepatocyte culture"Journal of Hepatology. 31. 293-299 (1999)

[Publications] Hideko Ohono: "Human hepatitis B virus X protein augments the DNA binding of NF-IL6 through its basic-leucine zipper domain"Journal of Medical Virology. 58. 11-18 (1999)

[Publications] Shuichi Kaneko: "In Nagy Habib (eds): "Methods in Molecular Medicine""Gene therapy vectors harvoring AFP regulatory sequences: preparation of an adenoviral vector (in press).

[Publications] Shuichi Kaneko: "In Sudhir Srivastava (eds): "Molecular Pathology of Early Cancer""Liver Cancer. 9 (1999)

小林健一金沢大学, 医学部, 教授 (70019933)