1990 年度実績報告書

レトロウイルスを利用した癌関連遺伝子の探索とその発現・機能の解析

研究課題

研究課題/領域番号	02151078
研究機関	国立がんセンター
研究代表者	口野嘉幸国立がんセンター研究所, 生物物理部, 部長 (60124418)
研究分担者	高橋雅英名古屋大学, 医学部・病理学第2講座, 講師 (40183446) 竹縄忠臣東京都老人総合研究所, 生体情報部門, 部長 (40101315) 竹家達夫京都大学, 化学研究所, 助教授 (60112330) 野田亮癌研究会癌研究所, ウイルス腫瘍部, 部長 (30146708) 西澤誠東京大学, 医科学研究所・癌ウイルス研究部, 助手 (30192248)
キーワード	癌遺伝子 / 癌抑制遺伝子 / maf遺伝子 / sーmyc遺伝子 / Krevー1遺伝子 / bek遺伝子 / ホスホリパ-ゼCγ2
研究概要	新規癌遺伝子および癌抑制遺伝子の探索という本研究班の中心テ-マに添って、この1年間各班員の精力的な研究が進められてきた。本班の研究成果のうち特筆すべきものとしては次のようなものが挙げられる: 1).トリ筋腱膜繊維腫発症の原因遺伝子としてvーmafが単離され、続いてヒトおよびトリ細胞に含まれるcーmaf遺伝子、さらにはmaf関連遺伝子の一つmafBが単離され、それらの構造解析が行われた。その結果、maf遺伝子産物はロイシンジッパ-構造をもつDNA結合蛋白質で、ホモ二量体、またはmafBとの間でヘテロ二量体を形成し、胚発生の段階で重要な役割をなしていることが明らかとなってきた(西澤)。2).ラットから新規myc関連遺伝子sーmycが単離され、その構造と機能の一部が明らかにされた。sーmyc遺伝子はイントロンーエキソン構造をもたない新しいタイプのmyc関連遺伝子で、その発現は、neu遺伝子の活性化によって癌化したラットの神経系腫瘍細胞RT4ーACのもつ造腫瘍性を抑制する(口野)。3).ヒト癌抑制遺伝子として単離されたKrevー1遺伝子の、詳細な構造と機能との関係について検討が加えられた。その結果、Krevー1蛋白質も他のras蛋白質同様、GTP/GDP交換反応によって癌抑制活性が制御されていること、同蛋白質のN末端から12,30,31番目のアミノ酸残基周辺の特異構造が癌抑制能の発現に重要であることなどが明らかとなった(野田)。4).チロシンキナ-ゼ活性をもち、FGFレセプタ-様構造をもつ新規遺伝子bek、およびその関連遺伝子brkがトリから単離された(竹家)。5).src類似構造をもつ新規蛋白質ホスホリパ-ゼCγ2に対する遺伝子が単離され、その発現と細胞増殖および癌化との関係が検討された(竹縄)。6).protoーret蛋白質に対する抗体が作成され、ret遺伝子の発現と細胞の癌化との関係について調べられた(高橋)。

研究成果

(36件)

すべてその他

すべて文献書誌 (36件)

[文献書誌] Nishizawa,M.: "vー<maf>___ー,a viral oncogene that encodes a “leucine zipper" motif." Proc.Natl.Acad.Sci.USA. 86. 7711-7715 (1989)
[文献書誌] Kawai,S.: "A variant SchmidtーRuppin Strain of Rous sarcoma virus with increased affinity for mammalina cells." Jpn.J.Cancer Res.80. 1179-1185 (1989)
[文献書誌] Semba,K.: "Transformation of chicken embryo fibroblast cells by avian retroviruses containing the human <fyn>___ー gene and its mutated genes." Mol.Cell.Biol.10. 3095-3104 (1990)
[文献書誌] Yamakawa,A.: "Molecular cloning and sequencing of cDNA encoding the phosphatidylinositol kinase from rat brain." J.Biol.Chem.
[文献書誌] Sugiyama,A.: "Isolation and characterization of sー<myc>___ー,a member of the rat myc gene family." Proc.Natl.Acad.Sci.USA. 86. 9144-9148 (1989)
[文献書誌] Lee,S.Y.: "Point mutation of the <neu>___ー gene in rat neural tumor RT4ーAC cells:Suppression of tumorigenicity by sーMyc." Jpn.J.Cancer Res.81. 1085-1088 (1990)
[文献書誌] Kitayama,H.: "Ge<net>___ーic analysis of the Krevー1 gene:Potentiation of its tumor suppressor activity by specific pont mutations." Proc.Natl.Acad.Sci.USA. 87. 4284-4288 (1990)
[文献書誌] Kitayama,H.: "A domain responsible for the transformation suppressor activity in Krevー1 protein." Jpn.J.Cancer Res.81. 445-448 (1990)
[文献書誌] Zhang,K.: "Identification of small clusters of divergent amino acids that mediate the opposing effects of <ras>___ー and K<rev>___ーー1." Science. 249. 162-165 (1990)
[文献書誌] Noda,M.: "Expression cloning of tumor suppressor genes:a guide for optimists." Mol.Carcinogenes. 3. 251-253 (1990)
[文献書誌] Hirota,Y.: "Nucleotide and deduced amino acid se<que>___ーnces of chiken lactate dehydrogenaseーA." Nucleic Acids Res.18. 6432 (1990)
[文献書誌] Sato,E.: "Ovarian glycosaminoglycans potentiate angiogenic activity of epidermal growth factor in mice." Endocrinology.
[文献書誌] Kato,M.: "Purification and characterization of membraneーbound and cytosolic forms of diacylglycerol kinase from rat brain." J.Biol.Chem.265. 794-800 (1990)
[文献書誌] Homma,Y.: "Isolation and characterization of a γーtype phosphoinositide specific phospholipase C." Biochem.J.269. 13-18 (1990)
[文献書誌] Takenawa,T.: "Properties of phospholipase C isozymes." Methods in Enzymol.197. 511-518 (1990)
[文献書誌] Shibasaki,F.: "Two types of phophatidylinositol kinase from bovine thymus:mononer and heterodimer form." J.Biol.Chem.
[文献書誌] Iwamoto,T.: "Oncogenicity of the <ret>___ー transforming gene in MMTV/<ret>___ー transgenic mice." Oncogene. 5. 553-542 (1990)
[文献書誌] Kikuchi,T.: "Nuclear localization of antigens detected by a monoclonal antibody against a synthetic peptide of <rfp>___ー finger protein." Hybridoma. 9. 189-200 (1990)
[文献書誌] Yokoi,T.: "Characterization of cell fusion in XC cells induced by <Suncus murinus>___ー mammary tumor virus." Archives of Virology. 115. 267-276 (1990)
[文献書誌] Takahashi,M.: "Identification of the <ret>___ー protoーoncogene products in neuroblastoma and leukemia cells." Oncogene.
[文献書誌] Nomura,N.: "Isolation of human cDNA clones of <ski>___ー and the <ski>___ーーrelated gne,<sno>___ー." Nucleic Acids Res.17. 5489-5500 (1989)
[文献書誌] Matsui,M.: "Isolation of human <fos>___ーーrelated genes and their expression during monocytemacrophage differentiation." Oncogene. 5. 249-255 (1990)
[文献書誌] Mizuguchi,G.: "DNA binding activity and transcriptional activator function of the human Bーmyc protein compared with cー<myc>___ー." J.Biol.Chem.265. 9280-9284 (1990)
[文献書誌] Nomura,N.: "Isolation of human cCNA clones of <jun>___ーーrelated genes,<jun>___ーーB and <jun>___ーーD." Nucleic Acids Res.18. 3047-3048 (1990)
[文献書誌] Date,T.: "Construction of Escherichia coli vectors for expression and mutagenesis:synthesis of human cーMyc protein that is initiated at a nonーAUG codon in exon 1." Gene. 90. 141-144 (1990)
[文献書誌] Momozaki,N.: "Selective syncytium formation by murine leukemia virus in rat 3Y1 fibroblasts transformed by adenovirus type 12 or its E1A gene." Arch.Virol.115. 123-126 (1990)
[文献書誌] Momozaki,N.: "Suppression of murine leukemia virusーmediated 3Y1 cells fusion by expression of mouse MHC class I." Arch.Virol.
[文献書誌] Kitajima,Y.: "Monoclonal antibodies recognizing aminoーterminal regions of human aldolase A:Probes to detect conformational changes of the enzyme." J.Biochem.
[文献書誌] Katoh,S.: "Identification of sequences responsible for positive and negative regulation by E1A in the promoter of Hー2K^<bme> class 1 MHC gene." EMBO J.9. 127-135 (1990)
[文献書誌] Shiroki,K.: "Tandemly repeated hexamer sequences within the beta interferon promoter can function as an inducible regulatory element in the activation by the adenovirus E1Bー19K protein." J.Virol.64. 3063-3068 (1990)
[文献書誌] Hiraizumi,S.: "Transfection with fragments of the adenovirus 12 gene induces tumorigenicityーassociated alteration of Nーlinked sugar chains in rat cells." Arch.Bioch.Bioph.280. 9-91 (1990)
[文献書誌] Sanai,Y.: "Expression of ganglioside GD_3 synthase activity in rat 3Y1 cells by adenovirus E1A gene." J.Biochem.
[文献書誌] Kim,D.W.: "Use of the human elongation factor la promoter as a versatile expression system." Gene. 91. 217-223 (1990)
[文献書誌] Kuchino,Y.,: "Isolation of the rat sーmyc gene having tumor suppressing activity.<in>___ー Genetic Basis for Carcinogenesis:Tumor Suppressor Genes and Oncogenes." (ed.)A.Knudson,Jr.et al.Japan Sci.Soc.Press,Tokyo/Vne Science Press,Utrecht., 7 (1990)
[文献書誌] Hirota,Y.: "Growth stimulation and gene expression.In “Control of cell growth and division"" (ed.)A.Ishihama,& H.Yoshikawa.Jpn.Sci.Soc.Press.Tokyo/SpringerーVerlag,Berlin., 21 (1990)
[文献書誌] Hirota,Y.: "Elevated expression of chicken lactate dehydrogenaseーA gene in transformed cells and characterization of its promoter region.In “Proceedings of Second International Mochida Memorial Symposium on Gene Expression""

1990 年度 実績報告書

レトロウイルスを利用した癌関連遺伝子の探索とその発現・機能の解析

研究代表者

口野 嘉幸 国立がんセンター研究所, 生物物理部, 部長 (60124418)

研究成果

[文献書誌] Nishizawa,M.: "vー<maf>___ー,a viral oncogene that encodes a “leucine zipper" motif." Proc.Natl.Acad.Sci.USA. 86. 7711-7715 (1989)

[文献書誌] Kawai,S.: "A variant SchmidtーRuppin Strain of Rous sarcoma virus with increased affinity for mammalina cells." Jpn.J.Cancer Res.80. 1179-1185 (1989)

[文献書誌] Semba,K.: "Transformation of chicken embryo fibroblast cells by avian retroviruses containing the human <fyn>___ー gene and its mutated genes." Mol.Cell.Biol.10. 3095-3104 (1990)

[文献書誌] Yamakawa,A.: "Molecular cloning and sequencing of cDNA encoding the phosphatidylinositol kinase from rat brain." J.Biol.Chem.

[文献書誌] Sugiyama,A.: "Isolation and characterization of sー<myc>___ー,a member of the rat myc gene family." Proc.Natl.Acad.Sci.USA. 86. 9144-9148 (1989)

[文献書誌] Lee,S.Y.: "Point mutation of the <neu>___ー gene in rat neural tumor RT4ーAC cells:Suppression of tumorigenicity by sーMyc." Jpn.J.Cancer Res.81. 1085-1088 (1990)

[文献書誌] Kitayama,H.: "Ge<net>___ーic analysis of the Krevー1 gene:Potentiation of its tumor suppressor activity by specific pont mutations." Proc.Natl.Acad.Sci.USA. 87. 4284-4288 (1990)

[文献書誌] Kitayama,H.: "A domain responsible for the transformation suppressor activity in Krevー1 protein." Jpn.J.Cancer Res.81. 445-448 (1990)

[文献書誌] Zhang,K.: "Identification of small clusters of divergent amino acids that mediate the opposing effects of <ras>___ー and K<rev>___ーー1." Science. 249. 162-165 (1990)

[文献書誌] Noda,M.: "Expression cloning of tumor suppressor genes:a guide for optimists." Mol.Carcinogenes. 3. 251-253 (1990)

[文献書誌] Hirota,Y.: "Nucleotide and deduced amino acid se<que>___ーnces of chiken lactate dehydrogenaseーA." Nucleic Acids Res.18. 6432 (1990)

[文献書誌] Sato,E.: "Ovarian glycosaminoglycans potentiate angiogenic activity of epidermal growth factor in mice." Endocrinology.

[文献書誌] Kato,M.: "Purification and characterization of membraneーbound and cytosolic forms of diacylglycerol kinase from rat brain." J.Biol.Chem.265. 794-800 (1990)

[文献書誌] Homma,Y.: "Isolation and characterization of a γーtype phosphoinositide specific phospholipase C." Biochem.J.269. 13-18 (1990)

[文献書誌] Takenawa,T.: "Properties of phospholipase C isozymes." Methods in Enzymol.197. 511-518 (1990)

[文献書誌] Shibasaki,F.: "Two types of phophatidylinositol kinase from bovine thymus:mononer and heterodimer form." J.Biol.Chem.

[文献書誌] Iwamoto,T.: "Oncogenicity of the <ret>___ー transforming gene in MMTV/<ret>___ー transgenic mice." Oncogene. 5. 553-542 (1990)

[文献書誌] Kikuchi,T.: "Nuclear localization of antigens detected by a monoclonal antibody against a synthetic peptide of <rfp>___ー finger protein." Hybridoma. 9. 189-200 (1990)

[文献書誌] Yokoi,T.: "Characterization of cell fusion in XC cells induced by <Suncus murinus>___ー mammary tumor virus." Archives of Virology. 115. 267-276 (1990)

[文献書誌] Takahashi,M.: "Identification of the <ret>___ー protoーoncogene products in neuroblastoma and leukemia cells." Oncogene.

[文献書誌] Nomura,N.: "Isolation of human cDNA clones of <ski>___ー and the <ski>___ーーrelated gne,<sno>___ー." Nucleic Acids Res.17. 5489-5500 (1989)

[文献書誌] Matsui,M.: "Isolation of human <fos>___ーーrelated genes and their expression during monocytemacrophage differentiation." Oncogene. 5. 249-255 (1990)

[文献書誌] Mizuguchi,G.: "DNA binding activity and transcriptional activator function of the human Bーmyc protein compared with cー<myc>___ー." J.Biol.Chem.265. 9280-9284 (1990)

[文献書誌] Nomura,N.: "Isolation of human cCNA clones of <jun>___ーーrelated genes,<jun>___ーーB and <jun>___ーーD." Nucleic Acids Res.18. 3047-3048 (1990)

[文献書誌] Date,T.: "Construction of Escherichia coli vectors for expression and mutagenesis:synthesis of human cーMyc protein that is initiated at a nonーAUG codon in exon 1." Gene. 90. 141-144 (1990)

[文献書誌] Momozaki,N.: "Selective syncytium formation by murine leukemia virus in rat 3Y1 fibroblasts transformed by adenovirus type 12 or its E1A gene." Arch.Virol.115. 123-126 (1990)

[文献書誌] Momozaki,N.: "Suppression of murine leukemia virusーmediated 3Y1 cells fusion by expression of mouse MHC class I." Arch.Virol.

[文献書誌] Kitajima,Y.: "Monoclonal antibodies recognizing aminoーterminal regions of human aldolase A:Probes to detect conformational changes of the enzyme." J.Biochem.

[文献書誌] Katoh,S.: "Identification of sequences responsible for positive and negative regulation by E1A in the promoter of Hー2K^<bme> class 1 MHC gene." EMBO J.9. 127-135 (1990)

[文献書誌] Shiroki,K.: "Tandemly repeated hexamer sequences within the beta interferon promoter can function as an inducible regulatory element in the activation by the adenovirus E1Bー19K protein." J.Virol.64. 3063-3068 (1990)

[文献書誌] Hiraizumi,S.: "Transfection with fragments of the adenovirus 12 gene induces tumorigenicityーassociated alteration of Nーlinked sugar chains in rat cells." Arch.Bioch.Bioph.280. 9-91 (1990)

[文献書誌] Sanai,Y.: "Expression of ganglioside GD_3 synthase activity in rat 3Y1 cells by adenovirus E1A gene." J.Biochem.

[文献書誌] Kim,D.W.: "Use of the human elongation factor la promoter as a versatile expression system." Gene. 91. 217-223 (1990)

[文献書誌] Kuchino,Y.,: "Isolation of the rat sーmyc gene having tumor suppressing activity.<in>___ー Genetic Basis for Carcinogenesis:Tumor Suppressor Genes and Oncogenes." (ed.)A.Knudson,Jr.et al.Japan Sci.Soc.Press,Tokyo/Vne Science Press,Utrecht., 7 (1990)

[文献書誌] Hirota,Y.: "Growth stimulation and gene expression.In “Control of cell growth and division"" (ed.)A.Ishihama,& H.Yoshikawa.Jpn.Sci.Soc.Press.Tokyo/SpringerーVerlag,Berlin., 21 (1990)

[文献書誌] Hirota,Y.: "Elevated expression of chicken lactate dehydrogenaseーA gene in transformed cells and characterization of its promoter region.In “Proceedings of Second International Mochida Memorial Symposium on Gene Expression""

1990 年度実績報告書

口野嘉幸国立がんセンター研究所, 生物物理部, 部長 (60124418)

[文献書誌] Zhang,K.: "Identification of small clusters of divergent amino acids that mediate the opposing effects of <ras>_ー and K<rev>_ーー1." Science. 249. 162-165 (1990)

[文献書誌] Iwamoto,T.: "Oncogenicity of the <ret>_ー transforming gene in MMTV/<ret>_ー transgenic mice." Oncogene. 5. 553-542 (1990)

[文献書誌] Nomura,N.: "Isolation of human cDNA clones of <ski>_ー and the <ski>_ーーrelated gne,<sno>___ー." Nucleic Acids Res.17. 5489-5500 (1989)

[文献書誌] Nomura,N.: "Isolation of human cCNA clones of <jun>_ーーrelated genes,<jun>_ーーB and <jun>___ーーD." Nucleic Acids Res.18. 3047-3048 (1990)