2001 Fiscal Year Annual Research Report

発がんと発がん防御の基礎的研究

Research Project

Project/Area Number	11178101
Research Institution	Research Institute, International Medical Center of Japan
Principal Investigator	笹月健彦国立国際医療センター, 研究所, 所長 (50014121)
Co-Investigator(Kenkyū-buntansha)	鎌滝哲也北海道大学, 大学院・薬学研究科, 教授 (00009177) 野田哲夫東北大学, 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) 伊藤恭悟久留米大学, 医学部, 教授 (50125499)
Keywords	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
Research Abstract	本特定領域研究「発がんと防御」は、総括班1班、計画研究55班、公募研究111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分野と2つの委員会を設定した。 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、「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の支援のための委員会」、「個体レベルでの新しい病理形態学的がん研究の推進と支援に関する委員会」。「がん特定」のその他の領域と連携して、平成13年7月、平成14年2月に研究代表者会議とシンポジウムを開催し、「発がんと防御」からも卓越した研究成果を挙げている研究者が発表を行った。これらをひと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。又、平成12年度の研究課題の評価と平成14年度の計画研究の選定を行った。

Research Products
(18 results)

All Other

All Publications (18 results)

[Publications] Hasegawa S: "Apoptosis in neural crest cells by functional loss of APC tumor suppressor gene"Proc. Natl. Acad. Sci. USA. 99. 297-302 (2002)
[Publications] Shimura T.: "p53 dependent S phase damage checkpoint and pronuclear crosstalk in mouse zygotes with X-irradiated sperm"Mol. Cell. Biol.. 22. 2220-2228 (2002)
[Publications] Oono T: "Organ-specific autoimmunity in mice whose T cell repertoire is shaped by a single antigenic peptide"J. Clin. Invest.. 108. 1589-1596 (2001)
[Publications] Fukui Y: "Hematopoietic cell-specific CDM family protein DOCK2 is essential for lymphocyte migration"Nature. 412. 826-831 (2001)
[Publications] Sakai K: "Identification of susceptibility loci for autoimmune thyroid disease to 5q31-q33 and Hashimoto's thyroiditis to 8q23-q24 by multipoint affected sib-pair linkage analysis in Japan"Hum. Mol. Genet.. 10. 1379-1386 (2001)
[Publications] Hoque T: "Human chromatid cohesin component hRad21 is phosphorylated in M phase and associated with metaphase centromeres"J. Biol. Chem.. 276. 5059-5067 (2001)
[Publications] Ohki R: "In vitro reconstitution of the end-replication problem"Mol. Cell. Biol.. 21. 5753-5766 (2001)
[Publications] Kobayashi T: "A germ-line Tsc1 mutation causes tumor development and embryonic lethality that are similar, but not identical to, those caused by Tsc2 mutation in mice"Proc. Natl. Acad. Sci. USA.. 98. 8762-8767 (2001)
[Publications] Yao Y: "Identification of a PDZ domain containing golgi protein GOPC, as an interaction partner of frizzled"Biochem. Biophys. Res. Commun.. 286. 771-778 (2001)
[Publications] Ariyoshi, N: "A novel single nucleotide polymorphism altering stability and activity of CYP2A6"Biochem. Biophys. Res. Commun.. 281. 810-814 (2001)
[Publications] Muto, S: "Inhibition by green tea catechins of metabolic activation of procarcinogens by human cytochrome P450"Mutat. Res.. 479. 197-206 (2001)
[Publications] Yamada A: "Multidrug resistance-associated protein 3 is a tumor rejection antigen recognized by HLA-A2402-restricted cytotoxic T lymphocytes"Cancer Research. 61. 6459-6466 (2001)
[Publications] Ito M: "Molecular basis of T cell-mediated recognition of pancreatic cancer cells"Cancer Research. 61. 2038-2046 (2001)
[Publications] Okamura S: "p53DINP1, a p53-inducible gene, regulates p53-dependent apoptosis"Molecular Cell. 8. 85-94 (2001)
[Publications] Watashi K: "Cytoplasmic localization is important for transcription factor nuclear factor-kappa B activation by hepatitis C virus core protein through its amino terminal region"Virology. 286. 391-402 (2001)
[Publications] Noguchi T.: "Effects of mutation in hepatitis C virus nonstructural protein 5A on interferon resistance mediated by inhibition of PKR kinase activity in mammalian cells"Microbiol. Immunol.. 45. 829-840 (2001)
[Publications] Jimbo, T..: "Link between the Tumor Suppressor APC and the Kinesin Superfamily of Proteins"Nature Cell Biol. (in press.). (2001)
[Publications] Fukamachi K: "Rat neuronal leucine-rich repeat protein-3 : cloning and regulation of the gene expression"Biochem. Biophys. Res. Commun.. 287. 257-263 (2001)

2001 Fiscal Year Annual Research Report

発がんと発がん防御の基礎的研究

Principal Investigator

笹月 健彦 国立国際医療センター, 研究所, 所長 (50014121)

Research Products

[Publications] Hasegawa S: "Apoptosis in neural crest cells by functional loss of APC tumor suppressor gene"Proc. Natl. Acad. Sci. USA. 99. 297-302 (2002)

[Publications] Shimura T.: "p53 dependent S phase damage checkpoint and pronuclear crosstalk in mouse zygotes with X-irradiated sperm"Mol. Cell. Biol.. 22. 2220-2228 (2002)

[Publications] Oono T: "Organ-specific autoimmunity in mice whose T cell repertoire is shaped by a single antigenic peptide"J. Clin. Invest.. 108. 1589-1596 (2001)

[Publications] Fukui Y: "Hematopoietic cell-specific CDM family protein DOCK2 is essential for lymphocyte migration"Nature. 412. 826-831 (2001)

[Publications] Sakai K: "Identification of susceptibility loci for autoimmune thyroid disease to 5q31-q33 and Hashimoto's thyroiditis to 8q23-q24 by multipoint affected sib-pair linkage analysis in Japan"Hum. Mol. Genet.. 10. 1379-1386 (2001)

[Publications] Hoque T: "Human chromatid cohesin component hRad21 is phosphorylated in M phase and associated with metaphase centromeres"J. Biol. Chem.. 276. 5059-5067 (2001)

[Publications] Ohki R: "In vitro reconstitution of the end-replication problem"Mol. Cell. Biol.. 21. 5753-5766 (2001)

[Publications] Kobayashi T: "A germ-line Tsc1 mutation causes tumor development and embryonic lethality that are similar, but not identical to, those caused by Tsc2 mutation in mice"Proc. Natl. Acad. Sci. USA.. 98. 8762-8767 (2001)

[Publications] Yao Y: "Identification of a PDZ domain containing golgi protein GOPC, as an interaction partner of frizzled"Biochem. Biophys. Res. Commun.. 286. 771-778 (2001)

[Publications] Ariyoshi, N: "A novel single nucleotide polymorphism altering stability and activity of CYP2A6"Biochem. Biophys. Res. Commun.. 281. 810-814 (2001)

[Publications] Muto, S: "Inhibition by green tea catechins of metabolic activation of procarcinogens by human cytochrome P450"Mutat. Res.. 479. 197-206 (2001)

[Publications] Yamada A: "Multidrug resistance-associated protein 3 is a tumor rejection antigen recognized by HLA-A2402-restricted cytotoxic T lymphocytes"Cancer Research. 61. 6459-6466 (2001)

[Publications] Ito M: "Molecular basis of T cell-mediated recognition of pancreatic cancer cells"Cancer Research. 61. 2038-2046 (2001)

[Publications] Okamura S: "p53DINP1, a p53-inducible gene, regulates p53-dependent apoptosis"Molecular Cell. 8. 85-94 (2001)

[Publications] Watashi K: "Cytoplasmic localization is important for transcription factor nuclear factor-kappa B activation by hepatitis C virus core protein through its amino terminal region"Virology. 286. 391-402 (2001)

[Publications] Noguchi T.: "Effects of mutation in hepatitis C virus nonstructural protein 5A on interferon resistance mediated by inhibition of PKR kinase activity in mammalian cells"Microbiol. Immunol.. 45. 829-840 (2001)

[Publications] Jimbo, T..: "Link between the Tumor Suppressor APC and the Kinesin Superfamily of Proteins"Nature Cell Biol. (in press.). (2001)

[Publications] Fukamachi K: "Rat neuronal leucine-rich repeat protein-3 : cloning and regulation of the gene expression"Biochem. Biophys. Res. Commun.. 287. 257-263 (2001)

笹月健彦国立国際医療センター, 研究所, 所長 (50014121)