2000 年度実績報告書

発がんと発がん防御の基礎的研究

研究課題

研究課題/領域番号	11178101
研究種目	特定領域研究(C)
研究機関	九州大学
研究代表者	笹月健彦九州大学, 生体防御医学研究所, 教授 (50014121)
研究分担者	鎌滝哲也北海道大学, 大学院・薬学研究科, 教授 (00009177) 野田哲生東北大学, 大学院・医学系研究科, 教授 (10183550) 石川冬木東京工業大学, 大学院・生命理工学研究科, 教授 (30184493) 中村祐輔東京大学, 医科学研究所, 教授 (70217909) 伊東恭悟久留米大学, 医学部, 教授 (50125499)
キーワード	がん / 遺伝子 / 環境要因 / 多段階発がん / 家系 / 免疫 / 発生工学 / 染色体
研究概要	本特定領域研究「発がんと防御」は、総括班1班、計画研究42班、公募研究126班より構成され、発がんの分子機構の解明を第一の目標とし、第二に細胞のがん化防御およびがん化した細胞の排除機構の解明を目指し、併せてがん研究の最終目標であるがん克服のための道を拓くことを目的とした。研究の標的を分子・細胞、個体、人類集団・家系、にそれぞれ設定し、遺伝子および染色体の構造の安定性と機能発現のダイナミクスに関する恒常性維持機構、内的外的発がん要因によるこれらのゲノム維持機構の破綻と細胞のがん化の関連、新しい発がん関連遺伝子の同定および既知遺伝子も含めたこれら遺伝子群の変異に引き続く多段階発がんの分子細胞生物学的機構、を解明することを目指し、さらに生体が備え持つ数々の恒常性維持機構がどのように細胞のがん化を防ぎ、どのようにがん化した細胞を排除し得るか、を分子レベルで解明することを目指し、研究を推進した。それらを達成するために、以下の5分野を設定した。 A01:細胞のがん化機構に関する研究、A02:がん関連遺伝子/発がん環境要因と発がんおよびがん悪性化の研究、A03:遺伝的高発がん集団に関する研究、A04:細胞のがん化防御に関する研究、A05:がん免疫の分子機構に関する研究平成12年度は以下のような活動を行った。 (1)シンポジウム:「がん特定」のその他5領域と連携して、平成12年6月、平成13年2月にシンポジウムを開催し、「発がんと防御」の分野で卓越した研究成果を挙げている研究者が発表を行った。 (2)ワークショップ:「発がんと防御」領域の全ての研究代表者が参加し、かつ全員が発表を行うワークショップを平成12年7月に開催した。これを一つの機会として各研究者間の交流、研究協力の実がはかられた。 (3)平成13年度の計画研究を慎重に検討し、設定した。 (4)PD、DCコースの研究者の選定を行った。 (5)「各種劣性遺伝病原因遺伝子ヘテロ接合保因者における発がん感受性の研究」のための全国調査、患者およびその家族由来の細胞バンク支援のための委員会(委員長・丹羽太貫)が開始され、また、平成13年より、実験動物を用いた病理形態学に裏打ちされたがん研究の推進と支援に関する委員会(委員長:野田哲生)が総括班に設定されることが決定した。

研究成果
(24件)

すべてその他

すべて文献書誌 (24件)

[文献書誌] Wataya M et al.: "Comparative analysis of HLA restriction and cytokine production of hepatitis B surface antigen-specific cells from low-and high-antibody responders in vaccinated humans."Journal of Human Genetics. (in press). (2001)
[文献書誌] Hamaguchi K et al.: "Analysis of tumor necrosis factor-alpha promoter polymorphism in type 1 diabetes : HLA-B and DRB1 alleles are primarily associated with the disease in Japanese"Tissue Antigens. 55. 10-16 (2000)
[文献書誌] Fukui Y et al.: "Diversity of T cell repertoire shaped by a single peptide ligand is critically affected by its amino acid residue at a T cell receptor contact."Proceedings of the National Academy of Sciences, USA. 97. 13760-13765 (2000)
[文献書誌] Toh H et al.: "Magnitude of structural changes of the T-cell receptor binding regions determine the strength of T-cell antagonism : molecular dynamics simulations of HLA-DR4(DRB1^*0405) complexed with analogue peptide."Protein Engineering. 13. 423-429 (2000)
[文献書誌] Ries S et al.: "Opposing effects of Ras on p53 : transcriptional activation of mdm2 and induction of p19^<ARF>."Cell. 103. 321-330 (2000)
[文献書誌] Shirasawa S et al.: "Rnx deficiency results in congenital central hypoventilation."Nature Genetics. 24. 287-290 (2000)
[文献書誌] Kawamura K et al.: "HLA-DR2-restricted responses to proteolipid protein 95-116 peptide cause autoimmune encephalitis in transgenic mice."Journal of Clinical Investigation. 105. 977-984 (2000)
[文献書誌] Baba I et al.: "Involvement of deregulated epiregulin expression in tumorigenesis in vivo through activated Ki-Ras signaling pathway in human colon cancer cells."Cancer Research. 60. 6886-6889 (2000)
[文献書誌] Hoque MT et al.: "Human Chromatid Cohesin Component hRad21 Is Phosphorylated in M Phase and Associated with Metaphase Centromeres."Journal of Biological Chemistry. 16. 5059-5067 (2001)
[文献書誌] Tatematsu KI et al.: "MBD2-MBD3 complex binds to hemi-methylated DNA and forms a complex containing DNMT1 at the replication foci in late S phase."Genes to Cells. 5. 677-688 (2000)
[文献書誌] Minowa O et al.: "Mmh/Ogg1 gene inactivation results in accumulation of 8-hydroxyguanine in mice."Proceedings of the National Academy of Sciences, USA. 97. 4156-4161 (2000)
[文献書誌] Kushida H et al.: "Metabolic activation of N-alkylnitrosamines in genetically engineered Salmonella typhimurium expressing CYP2E1 or CYP2A6 to gether with human NADPH-cytochrome P450 reductase."Carcinogenesis. 21. 1227-1232 (2000)
[文献書誌] Kawano K et al.: "Identification of a new endoplasmic reticulum-resident protein recognized by the HLA-A24-restricted tumor infiltrating lymphocytes of lung cancer."Cancer Research. 60. 3550-3558 (2000)
[文献書誌] Nishizaka S et al.: "A new tumor-rejection antigen recognized by cytotoxic T lymphocytes infiltrating into a lung adenocarcinoma."Cancer Research. 60. 4830-4837 (2000)
[文献書誌] Satoh S et al.: "Axin mutations in hepatocellular carcinomas, and growth suppression in cancer cells by virus-mediated transfer of wild-type Axin."Nature Genetics. 24. 245-250 (2000)
[文献書誌] Tanaka H et al.: "A ribonucleotide reductase gene involved in a p53 dependent DNA damage checkpoint."Nature. 404. 42-49 (2000)
[文献書誌] Tago K et al.: "Inhibition of Wnt signaling by ICAT, a Novel b-catenin-interacting Protein."Genes and Development. 14. 1741-1749 (2000)
[文献書誌] Kawasaki Y et al.: "Asef, a Link between the Tumor Suppressor APC and G-protein Signaling."Science. 289. 1194-1197 (2000)
[文献書誌] Asamoto A et al.: "Transgenic rats carrying human c-Ha-ras proto-oncogenes are highly susceptible to N-Methyl-N-nitrosourea mammary carcinogenesis."Carcinogenesis. 21. 243-249 (2000)
[文献書誌] Ota T et al.: "Transgenic rats carrying copies of the human c-Ha-ras proto-oncogene exhibit enhanced susceptibility to N-butyl-N-(4-hydroxybutyl) nitrosamine bladder carcinogenesis."Carcinogenesis. 21. 1391-1396 (2000)
[文献書誌] Niwa O et al.: "Untargeted mutation of the maternally derived mouse hypervariable minisatellite allele in F1 mice born to irradiated spermatozoa."Proceedings of the National Academy of Sciences, USA. 98. 1705-1710 (2001)
[文献書誌] Taga M et al.: "Icreased frequencies of gene and chromosome mutations after X-irradiation in mouse embryonal carcinoma cells transfected with the bcl-2 gene."Japanese Journal of Cancer Research. 91. 994-1000 (2000)
[文献書誌] Ariumi Y et al.: "HTLV-1 tax oncoprotein represses the p53-mediated trans-activation function through coactivator CBP sequestration."Oncogene. 19. 1491-1499 (2000)
[文献書誌] Kaida A et al.: "Functional impairment of p73 and p51, the p53-related proteins, by the human T-cell leukemia virus type 1 Tax oncoprotein."Oncogene. 19. 827-830 (2000)

2000 年度 実績報告書

発がんと発がん防御の基礎的研究

研究代表者

笹月 健彦 九州大学, 生体防御医学研究所, 教授 (50014121)

研究成果

[文献書誌] Wataya M et al.: "Comparative analysis of HLA restriction and cytokine production of hepatitis B surface antigen-specific cells from low-and high-antibody responders in vaccinated humans."Journal of Human Genetics. (in press). (2001)

[文献書誌] Hamaguchi K et al.: "Analysis of tumor necrosis factor-alpha promoter polymorphism in type 1 diabetes : HLA-B and DRB1 alleles are primarily associated with the disease in Japanese"Tissue Antigens. 55. 10-16 (2000)

[文献書誌] Fukui Y et al.: "Diversity of T cell repertoire shaped by a single peptide ligand is critically affected by its amino acid residue at a T cell receptor contact."Proceedings of the National Academy of Sciences, USA. 97. 13760-13765 (2000)

[文献書誌] Toh H et al.: "Magnitude of structural changes of the T-cell receptor binding regions determine the strength of T-cell antagonism : molecular dynamics simulations of HLA-DR4(DRB1^*0405) complexed with analogue peptide."Protein Engineering. 13. 423-429 (2000)

[文献書誌] Ries S et al.: "Opposing effects of Ras on p53 : transcriptional activation of mdm2 and induction of p19^<ARF>."Cell. 103. 321-330 (2000)

[文献書誌] Shirasawa S et al.: "Rnx deficiency results in congenital central hypoventilation."Nature Genetics. 24. 287-290 (2000)

[文献書誌] Kawamura K et al.: "HLA-DR2-restricted responses to proteolipid protein 95-116 peptide cause autoimmune encephalitis in transgenic mice."Journal of Clinical Investigation. 105. 977-984 (2000)

[文献書誌] Baba I et al.: "Involvement of deregulated epiregulin expression in tumorigenesis in vivo through activated Ki-Ras signaling pathway in human colon cancer cells."Cancer Research. 60. 6886-6889 (2000)

[文献書誌] Hoque MT et al.: "Human Chromatid Cohesin Component hRad21 Is Phosphorylated in M Phase and Associated with Metaphase Centromeres."Journal of Biological Chemistry. 16. 5059-5067 (2001)

[文献書誌] Tatematsu KI et al.: "MBD2-MBD3 complex binds to hemi-methylated DNA and forms a complex containing DNMT1 at the replication foci in late S phase."Genes to Cells. 5. 677-688 (2000)

[文献書誌] Minowa O et al.: "Mmh/Ogg1 gene inactivation results in accumulation of 8-hydroxyguanine in mice."Proceedings of the National Academy of Sciences, USA. 97. 4156-4161 (2000)

[文献書誌] Kushida H et al.: "Metabolic activation of N-alkylnitrosamines in genetically engineered Salmonella typhimurium expressing CYP2E1 or CYP2A6 to gether with human NADPH-cytochrome P450 reductase."Carcinogenesis. 21. 1227-1232 (2000)

[文献書誌] Kawano K et al.: "Identification of a new endoplasmic reticulum-resident protein recognized by the HLA-A24-restricted tumor infiltrating lymphocytes of lung cancer."Cancer Research. 60. 3550-3558 (2000)

[文献書誌] Nishizaka S et al.: "A new tumor-rejection antigen recognized by cytotoxic T lymphocytes infiltrating into a lung adenocarcinoma."Cancer Research. 60. 4830-4837 (2000)

[文献書誌] Satoh S et al.: "Axin mutations in hepatocellular carcinomas, and growth suppression in cancer cells by virus-mediated transfer of wild-type Axin."Nature Genetics. 24. 245-250 (2000)

[文献書誌] Tanaka H et al.: "A ribonucleotide reductase gene involved in a p53 dependent DNA damage checkpoint."Nature. 404. 42-49 (2000)

[文献書誌] Tago K et al.: "Inhibition of Wnt signaling by ICAT, a Novel b-catenin-interacting Protein."Genes and Development. 14. 1741-1749 (2000)

[文献書誌] Kawasaki Y et al.: "Asef, a Link between the Tumor Suppressor APC and G-protein Signaling."Science. 289. 1194-1197 (2000)

[文献書誌] Asamoto A et al.: "Transgenic rats carrying human c-Ha-ras proto-oncogenes are highly susceptible to N-Methyl-N-nitrosourea mammary carcinogenesis."Carcinogenesis. 21. 243-249 (2000)

[文献書誌] Ota T et al.: "Transgenic rats carrying copies of the human c-Ha-ras proto-oncogene exhibit enhanced susceptibility to N-butyl-N-(4-hydroxybutyl) nitrosamine bladder carcinogenesis."Carcinogenesis. 21. 1391-1396 (2000)

[文献書誌] Niwa O et al.: "Untargeted mutation of the maternally derived mouse hypervariable minisatellite allele in F1 mice born to irradiated spermatozoa."Proceedings of the National Academy of Sciences, USA. 98. 1705-1710 (2001)

[文献書誌] Taga M et al.: "Icreased frequencies of gene and chromosome mutations after X-irradiation in mouse embryonal carcinoma cells transfected with the bcl-2 gene."Japanese Journal of Cancer Research. 91. 994-1000 (2000)

[文献書誌] Ariumi Y et al.: "HTLV-1 tax oncoprotein represses the p53-mediated trans-activation function through coactivator CBP sequestration."Oncogene. 19. 1491-1499 (2000)

[文献書誌] Kaida A et al.: "Functional impairment of p73 and p51, the p53-related proteins, by the human T-cell leukemia virus type 1 Tax oncoprotein."Oncogene. 19. 827-830 (2000)

2000 年度実績報告書

笹月健彦九州大学, 生体防御医学研究所, 教授 (50014121)