1989 Fiscal Year Annual Research Report

癌化関連遺伝子の特異的発現機構

Research Project

Project/Area Number	01010007
Research Institution	Tohoku University
Principal Investigator	藤井義明東北大学, 理学部, 教授 (00098146)
Co-Investigator(Kenkyū-buntansha)	渡辺武九州大学, 生体防御医学研究所, 教授 (40028684) 長田重一大阪バイオサイエンス研究所, 部長 (70114428) 鈴木義昭基礎生物学研究所, 教授 (50132733) 西郷薫東京大学, 理学部, 教授 (50136454) 遠藤英也鳥取大学, 歯学部, 教授 (40037320)
Keywords	遺伝子発現 / エンハンサー / 核内因子 / 転写 / 癌細胞 / 制御領域 / メチル化 / 転移性因子
Research Abstract	本研究グループは癌細胞の遺伝子発現の異常の本質を明らかにする目的で編成された。本年の研究成果は次の通りである。酒井は肝癌におけるGSTpの異常発現は遺伝子上流の転写制御エレメントTREに働くcjunの発現によることを示した。また遠藤は癌化に伴い特異的に発現が誘導されることの多いレトロウィルス様遺伝子の発現誘導にはプロモーター領域の脱メチル化が関係している可能性を指摘した。一方堤は発癌に伴うアルドラーゼB遺伝子の発現停止は肝特異的な転写に協調的に働く二つのDNA要素(A,B)の中のB要素のメチル化によることを明らかにした。メチル化によってこの要素に働く転写因子の結合が阻害される。藤井はPー450遺伝子の制御領域に結合する因子のcDNAクローンを分離して、その構造解析より新しいDNA結合因子であることを示した。鈴木はフィブロイン遺伝子の転写制御にはホメオドメインを持つ複数の制御因子が関与していることを明らかにした。渡辺はIgGH鎖遺伝子にB細胞特異的発現に働く新しいDNA要素を見出し、長田はGーCSF遺伝子に三つの細胞特異的に働いてLPS刺激に応答する要素の存在を証明し、各々の要素に働く因子の分離精製を行なっている。西郷はDrosophilaの複眼形成異常の原因であるBarHI遺伝子の過剰発現はtranspossonの挿入によることを示唆した。岡田(典)は一次構造の比較から高等動物のretrotranspossonはtRNAを起源としていることを示唆した。岡田(信)はアザチロシンによる癌細胞の正常復帰誘導の機構を研究するために差ハイブリダイゼーションを行い正常復帰に特異的に出現するcDNAクローンを得て構造を行っている。若い研究者の榎森はPLaseCのcDNAの解析を行いSrc関連配列をもった新しい構造を明らかにし、岡田(雅)は新生ラットの脳にp60CーSrcに特異的なチロシンキナーゼの精製に成功した。島田はPー450 6βの異なった分子種が肝において成長ホルモンによって正あるいは負の制御されていることを示した。

Research Products

(18 results)

All Other

All Publications (18 results)

[Publications] Sogawa,K.: "Repression of Cytochrome P-450c Gene Expression by Cotransfection with Adenovirus Ela DNA." J.Biochem.181. 538-544 (1989)
[Publications] Lorence,M.C.: "Expression of a Full Length cDNA Encoding Bovine Adrenal Cytochrome P-450c21." Arch.Biochem.Biophys.273. 79-88 (1989)
[Publications] Nakamuta,M.: "Isolation and characterization of a family of rat endogenous retroviral sequences." Virus Genes. 3. 69-83 (1989)
[Publications] Okuda,A.: "Structural and functional analysis of an enhancer GPE-1 having a TPA responsive element-like sequence found in the rat GST-P gene." J.Biol.Chem.264. 16919-16926 (1989)
[Publications] Sakai,M.: "Structure and expression of the rat c-jun mRNA:Tissue distribution and increase during chemical hepatocarcinogenesis." Cancer Res.49. 5633-5637 (1989)
[Publications] Okuda,A.: "Functional cooperativity between two TPA responsive elements in undifferentiated F9 embryonal stem cell." EMBO J.
[Publications] Matsuno,K.: "Transcription signals and protein binding sites for sericin gene transcription in vitro." J.Biol.Chem.264. 18707-18713 (1989)
[Publications] Sindo-Okada,N.: "Permanent Conversion of Mouse and Human Cells Transformed by Activated ras and raf Genes to Apparently Normal Cells by Treatment with the Antibiotic Azatyrosine." Mol.Carcinogenesis.2. 159-167 (1989)
[Publications] Hui,C.-C.: "Enhancement of transcription from the Ad2 major late promoter by the upstream elements of the fibroin and sericin-1 genes in silk gland extracts." Gene. 85. 405-413 (1989)
[Publications] Tsutsumi K.: "Developmental Appearance of Transcription Factors That Regulate Liver-Specific Expression of the Rat Aldolase B Gene." Mol.Cell.Biol.9. 4923-4931 (1989)
[Publications] Nagata,S.: "Gene structure and function of granulocyte colony-stimulating factor." BioEssays. 4. 113-117 (1989)
[Publications] Shirafuji,N.: "Estimation of human granulocyte colony-stimulating factor in sera from normal healthy persons and patients with infectious and hematological disorders." Exp.Hematol.17. 116-119 (1989)
[Publications] Shirafuji,N.: "Granulocyte colony-stimulating factor stimulates human mature neutrophilic granulocytes to produce interferon-alpha." Blood. 75. 17-19 (1990)
[Publications] Matsuhashi,S.: "Preparation of monoclonal antibodies against nuclear antigens in DNA affinity prified protein fraction from chick embryo extract." Japan.J.Ext.Med.59. 139-147 (1989)
[Publications] Kitamura,D.: "Isolation and characterization of a novel human gene expressed specifically in the cells of hematopoietic lineage." Nucleic Acids Res.17. 9367-9379 (1989)
[Publications] Emori,Y.: "A second type of rat phosphoinositide-specieic phospholipase C containing a src-related sequence not essential for phosphoinositide-hydrolyzing activity." J.Biol.Chem.264. 21885-21890 (1989)
[Publications] Okada,M.: "A Protein Tyrosine Kinase Involved in Regulation of pp60^<c-src> Function." J.Biol.Chem.264. 20886-20893 (1989)
[Publications] Shimada,M.: "Suppression in the Expression of a Male-Specific Cytochrome P-450,P-450-male:Difference in the Effect of Chemical Inducers on P-450-Male mRNA and Protein in Rat Liver." Arch.Biochem.Biophys.270. 578-587 (1989)

1989 Fiscal Year Annual Research Report

癌化関連遺伝子の特異的発現機構

Principal Investigator

藤井 義明 東北大学, 理学部, 教授 (00098146)

Research Products

[Publications] Sogawa,K.: "Repression of Cytochrome P-450c Gene Expression by Cotransfection with Adenovirus Ela DNA." J.Biochem.181. 538-544 (1989)

[Publications] Lorence,M.C.: "Expression of a Full Length cDNA Encoding Bovine Adrenal Cytochrome P-450c21." Arch.Biochem.Biophys.273. 79-88 (1989)

[Publications] Nakamuta,M.: "Isolation and characterization of a family of rat endogenous retroviral sequences." Virus Genes. 3. 69-83 (1989)

[Publications] Okuda,A.: "Structural and functional analysis of an enhancer GPE-1 having a TPA responsive element-like sequence found in the rat GST-P gene." J.Biol.Chem.264. 16919-16926 (1989)

[Publications] Sakai,M.: "Structure and expression of the rat c-jun mRNA:Tissue distribution and increase during chemical hepatocarcinogenesis." Cancer Res.49. 5633-5637 (1989)

[Publications] Okuda,A.: "Functional cooperativity between two TPA responsive elements in undifferentiated F9 embryonal stem cell." EMBO J.

[Publications] Matsuno,K.: "Transcription signals and protein binding sites for sericin gene transcription in vitro." J.Biol.Chem.264. 18707-18713 (1989)

[Publications] Sindo-Okada,N.: "Permanent Conversion of Mouse and Human Cells Transformed by Activated ras and raf Genes to Apparently Normal Cells by Treatment with the Antibiotic Azatyrosine." Mol.Carcinogenesis.2. 159-167 (1989)

[Publications] Hui,C.-C.: "Enhancement of transcription from the Ad2 major late promoter by the upstream elements of the fibroin and sericin-1 genes in silk gland extracts." Gene. 85. 405-413 (1989)

[Publications] Tsutsumi K.: "Developmental Appearance of Transcription Factors That Regulate Liver-Specific Expression of the Rat Aldolase B Gene." Mol.Cell.Biol.9. 4923-4931 (1989)

[Publications] Nagata,S.: "Gene structure and function of granulocyte colony-stimulating factor." BioEssays. 4. 113-117 (1989)

[Publications] Shirafuji,N.: "Estimation of human granulocyte colony-stimulating factor in sera from normal healthy persons and patients with infectious and hematological disorders." Exp.Hematol.17. 116-119 (1989)

[Publications] Shirafuji,N.: "Granulocyte colony-stimulating factor stimulates human mature neutrophilic granulocytes to produce interferon-alpha." Blood. 75. 17-19 (1990)

[Publications] Matsuhashi,S.: "Preparation of monoclonal antibodies against nuclear antigens in DNA affinity prified protein fraction from chick embryo extract." Japan.J.Ext.Med.59. 139-147 (1989)

[Publications] Kitamura,D.: "Isolation and characterization of a novel human gene expressed specifically in the cells of hematopoietic lineage." Nucleic Acids Res.17. 9367-9379 (1989)

[Publications] Emori,Y.: "A second type of rat phosphoinositide-specieic phospholipase C containing a src-related sequence not essential for phosphoinositide-hydrolyzing activity." J.Biol.Chem.264. 21885-21890 (1989)

[Publications] Okada,M.: "A Protein Tyrosine Kinase Involved in Regulation of pp60^<c-src> Function." J.Biol.Chem.264. 20886-20893 (1989)

[Publications] Shimada,M.: "Suppression in the Expression of a Male-Specific Cytochrome P-450,P-450-male:Difference in the Effect of Chemical Inducers on P-450-Male mRNA and Protein in Rat Liver." Arch.Biochem.Biophys.270. 578-587 (1989)

藤井義明東北大学, 理学部, 教授 (00098146)