アポトーシス阻止に作用する遺伝子FAP-1の遺伝子

• 研究課題/領域番号: 08671250
• 研究種目: 基盤研究(C)
• 配分区分: 補助金
• 応募区分: 一般
• 研究分野: 血液内科学
• 研究機関: 自治医科大学
• 研究代表者: 畠 清彦 自治医科大学, 医学部, 助教授 (80192699)
• 研究分担者: 冨塚 浩 (富塚 浩) 自治医科大学, 医学部, 講師 (00285785) ; 照井 康仁 自治医科大学, 医学部, 講師 (10285786) ; 大月 哲也 自治医科大学, 医学部, 講師 (60275691) ; 星野 充明 自治医科大学, 医学部, 助手 (70275692) ; 角田 純一 自治医科大学, 医学部, 助手 (20245054)
• 研究期間 (年度): 1996 – 1998
• 研究課題ステータス: 完了 (1998年度)
• 配分額: 2,000千円 (直接経費: 2,000千円); 1998年度: 500千円 (直接経費: 500千円); 1997年度: 500千円 (直接経費: 500千円); 1996年度: 1,000千円 (直接経費: 1,000千円)
• キーワード: アポトーシス / FAP-1 / T細胞性白血病 / Fasリガンド / Fas / シグナル伝達 / HIV

研究概要

FAP-1(Fas-Associated Protein-1)は細胞死に関係する遺伝子のひとつであるが、血液幹細胞の1分画であるCD34陽性細胞でさらに分化マーカーによって4つの細分画に分けて細胞を集め、遺伝子の発現を検討した。FAP-1は顆粒球/マクロファージコロニー、赤芽球コロニーでは発現に差違を認めなかった。FAP-1はT細胞のアポトーシスに関与しているので、T細胞性白血病のアポトーシスの機序をさらに検討した。3つの蛋白が精製でき、1つは内皮細胞由来インターロイキン8(IL-8Eと略す)であった。内皮細胞とT細胞性白血病との相互作用を観察したところ、IL-8Eが放出され、アポトーシスが誘導された。この作用機序を検討中である。Fasリガンドによるアポトーシスは、T細胞が活性化されないと誘発されないことから、その作用機序としてFAP-1よりもFasリガンドに対するdecoy receptorの発現増強が関与している報告が出ており、検討が重要と考えられた。

研究成果

• [文献書誌] Shimura M, Hatake K, et al.: "Characterization of room temperature induced apoptosis in HL-60." FEBS Lett.417. 379-384 (1997)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] Yamada M, Hatake K, et al.: "Properties of murine stroma induced by M-CSF." J.Cell Physiol. 173. 1-9 (1997)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] Ohno R, Hatake K, et al.: "Human urinary macrophage colony-stimulating factor reduces the incidence and duration of febrile neutropenia and shortens the period required to finish three courses of intensive consolidation chemotherapy in acute myeloif leukemia." J Clin Oncol. 15. 2954-2965 (1997)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] Muroi K, Hatake K.et al.: "No CD117 expression in B progenitors in the regenerating bone marrow." Int J Hematol. 66. 245-247 (1997)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] Ohya K, Hatake K, et al: "SOCS-1/JAB/SSl-1 can bind to and suppress Tec protein-tyrosine kinase." J Biol Chem. 272. 27178-27182 (1997)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] Hatake K, Tomizuka H, et al.: "Rare but important adverse effects of all-trans retinoic acid in acute promyelocytic leukemia and their management." J Hematol. 66. 13-19 (1997)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] Ohtsuki T, Hatake K, et al.: "Expression of Src-like adapter protein mRNA is induced by all-trans retinoic acid." Biochem Biophys Res Comm.230. 81-84 (1997)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] Nakamura M, Hatake K, et al.: "Single glycosyltransferase, core 2 b1-6-N-acetylglucosamiyltransferase, regulates cell surface sialy-Lex expression level in humna pre-B lymphocytic leukemia cell line KM3 treated with phorbolester" J Biol Chem. 273. 26779-26789 (1998)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] Suzu S, Hatake K, et al.: "Identification of alternatively spliced transcripts encoding murine macrophage colony-stimulating factor." Biochem Biophys Res Comm. 245. 120-126 (1998)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] Yamashita Y, Hatake K, et al.: "Tec and JAK2 kinases cooperate to mediate cytokine-driven activation of c-fos transcription." Blood. 91. 1496-1507 (1998)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] Terui Y, Hatake K.: "Activated endothelial cells induces apoptosis in leukemic cells by endothelial interleukin-8." Blood. 92. 2672-2680 (1998)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] Terui Y, Hatake K.: "Identification of a novel apoptosis-inducing factor derived from leukemic cells : Endothelial interleukin-8, but not monocyte-derived, induces apoptosis in leukemic cells." Biochem Biophy Res Comm. 243. 407-411 (1998)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] Terui Y, Hatake K, et al.: "Bcl-X ls a Regulatory Factor of Apoptosis and Differentiation in Megakaryocytic Lineage Cells." Exp Hematol. 26. 236-244 (1998)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] Tomizuka H, Hatake K, et al.: "CD95 predicts responsiveness to tretinoin in acute promyelocytic leukemia." Int J Mol Med. 1. 207-211 (1998)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] Ikeda T, Hatake K, et al.: "IL-13 as well as IL-4 induces monocytes/macrophages and a monoblastic cell line(UG3)to differentiate into multinucleated giant cells in the presence of M-CSF." Biochem Biophys Res Comm. (in press.). (1999)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] Igarashi H, Hatake K, Tomizuka H, et al.: "High serum level of macrophage colony-stumlating factor and granulocytic colony-stimulating factor in Kawasaki disease." Brit J Haematol. (in press.). (1999)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] Tanaka-Douzono M, Hatake K, et al.: "The in vivo stimulatory effect of macrophage colony-stimulating factor on the number of stroma-initiating cells." J Cell Physiol. (in press.). (1999)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] Shimura M, Hatake K, et al.: "Micronuclei formation and aneuploidy induced by Vpr, an accessory gene of human immunodeficiency virus type 1." FASEB J. (in press.). (1999)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] Shimura M,Hatake K,et al.: "Characterization of room temperature induced apoptosis in HL-60." FEBS Lett.417. 379-384 (1997)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Yamada M,Hatake K,et al.: "Properties of murine stroma induced byM-CSF." J.Cell Physiol.173. 1-9 (1997)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Ohno R,Hatake K,et al.: "Human urinary macrophage colony-stimulating factor reduces the incidence and duration of febrile neutropenia and shortens the period required to finish three courses of intensive consolidation chemotherapy in acute myeloif leukemia." J Clin Oncol. 15. 2954-2965 (1997)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Muroi K,Hatake K,et al.: "No CD117 expression in B progenitors in the regenerating bone marrow." Int J Hematol.66. 245-247 (1997)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Ohya K,Hatake K,et al.: "SOCS-1/JAB/SSI-1 can bind to and suppress Tec protein-tyrosine kinase." J Biol Chem.272. 27178-27182 (1997)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Hatake K,Ohtsuki T,Tomizuka H,et al.: "Rare but important adverse effects of all-trans retinoic acid in acute promyelocytic leukemia and their management." Int J Hematol.66. 13-19 (1997)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Ohtsuki T,Hatake K,Tomizuka H,Terui Y,et al.: "Expression of Src-like adapter protein mRNA is induced by all-trans retinoic acid." Biochem Biophys Res Comm.230. 81-84 (1997)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Terui Y,Hatake K,et al.: "Activated endothelial cells induces apoptosis in leukemic cells by endothelial interleukin-8." Blood. 92. 2672-2680 (1998)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Muroi K,Hatake K,et al.: "CD56 expression in B cell neoplasm." Leukemia Res. (in press). (1998)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Suzu S,Hatake K,et al.: "Identification of alternatively spliced transcripts encoding murine macrophage colony-stimulating factor." Biochem Biophys Res Comm.245. 120-126 (1998)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Terui Y,Tomizuka H,Ohtsuki T,Hatake K.: "Identification of a novel apoptosis-inducing factor derived from leukemic cells : Endothelial interleukin-8, but not monocyte-derived, induces apoptosis in leukemic sells." Biochem Biophy Res Comm.243. 407-411 (1998)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Terui Y,Hatake K,et al.: "Bcl-X Is a Regulatory Factor of Apoptosis and Differentiation in Megakaryocytic Lineage Cells." Exp Hematol.26. 236-244 (1998)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Hatake K,Tomizuka H,Terui Y,et al.: "Apoptosis-gene expression in hematopoietic system : Normal and pathological conditions." Int J Mol Med.1. 121-129 (1998)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Tomizuka H,Hatake K,et al.: "CD95 predicts responsiveness to tretinoin in acute promyelocytic leukemia." Int J Mol Med.1. 207-211 (1998)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Kasahara T,Oda T,Hatake K,et al.: "IL-8 and MCP-1 production by a human glioblastoma cell line, T98G in coculture with monocytes : Requirement of mococytes-associated IL-1alpha." Eur Cytokine Net.9. 47-55 (1998)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Yamashita Y,Hatake K,et al.: "Tec and JAK2 kinases cooperate to mediate cytokine-driven activation of c-fos transcription." Blood. 91. 1496-1507 (1998)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Nakamura M,Hatake K,et al.: "Single glycosyltransferase, core 2 b1-6-N-acetylglucosamiyltransferase, regulates cell surface sialyl-Lex expression level in human pre-B lymphocytic leukemia cell line KM3 treated with phorbolester." J Biol Chem.273. 26779-26789 (1998)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Tanaka-Douzono M,Hatake K,et al.: "The in vivo stimulatory effect of macrophage colony-stimulating factor on the number of stroma-initiating cells." J Cell Physiol. (in press). (1998)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Igarashi, Hatake K,et al.: "High serum level of macrophage colony-stumlatingfactor and granulocytic colony-stimulating factor in Kawasaki disease." Brit J Haematol. (in press). (1999)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Shimura M,Hatake K,et al.: "Micronuclei formation and aneuploidy induced by Vpr, an accessory gene of human immunodeficiency virus type 1." FASEB.J. (in press). (1999)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Ikeda T,Hatake K,et al.: "IL-13 as well as IL-4 induces monocytes/macrophages and a monoblastic cell line (UG3) to differentiate into multinucleated giant cells in the presence of M-CSF." Biochem Biophys Res Comm.(in press). (1999)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Nakamura M,Hatake K,et al.: "Single glycosyltransferase,core 2 b1-6-N-acetylglucosamiyltransferase,regulates cell surface sialyl-Lex expression level in human pre-B lymphocytic leukemia cell line KM3 treated with phorbolester." J Biol Chem. 273. 26779-26789 (1998)
• [文献書誌] Suzu S,Hatake K,et al.: "Identification of alternatively spliced transcripts encoding murine macrophage colony-stimulating factor." Biochem Biophys Res Comm. 245. 120-126 (1998)
• [文献書誌] Yamashita Y,Hatake K,et al: "Tec and JAK2 kinases cooperate to mediate cytokine-driven activation of c-fos transcription." Blood. 91. 1496-1507 (1998)
• [文献書誌] Terui Y,Hatake K.: "Activated endothelial cells induces apoptosis in leukemic cells by endothelial interleukin-8." Blood. 92. 2672-2680 (1998)
• [文献書誌] Terui Y,Hatake K.: "Identification of a novel apoptosis-inducing factor derived from leukemic cells: Endothelial interleukin-8,but not monocyte-derived,induces apoptosis in leukemic cells." Biochem Biophy Res Comm. 243. 407-411 (1998)
• [文献書誌] Terui Y,Hatake K,et al.: "Bcl-X is a Regulatory Factor of Apoptosis and Differentiation in Megakaryocytic Lineage Cells." Exp Hematol. 26. 236-244 (1998)
• [文献書誌] Tomizuka H,Hatake K,et al.: "CD95 predicts responsiveness to tretinoin in acute promyelocytic leukemia." Int J Mol Med. 1. 207-211 (1998)
• [文献書誌] Ikeda T,Hatake K,et al.: "IL-13 as well as IL-4 induces monocytes/macrophages and a monoblastic cell line(UG3) to differentiate into multinucleated giant cells in the presence of M-CSF." Biochem Biophys Res Comm. (in press). (1999)
• [文献書誌] Igarashi H,Hatake K,Tomizuka H,et al.: "High serum level of macrophage colony-stumlating factor and granulocytic colony-stimulating factor in Kawasaki disease." Brit J Haematol. (in press). (1999)
• [文献書誌] Tanaka-Douzono M,Hatake K,et al.: "The in vivo stimulatory effet of macrophage colony-stimulating factor on th number of stroma-initiating cells." J Cell Physiol. (in press). (1999)
• [文献書誌] Shimura M,Hatake K,et al.: "Micronuclei formation and aneupioldy induced by Vpr,an accessory gene of human immunodeficiency virus type 1." FASEB J. (in press). (1999)
• [文献書誌] Terui Y.,Hatake K., et al.: "Identification of a novel apoptosis-inducing factor derived from leukemic cells:Endothelial interleukin-8,but not monocyte-derived,induces apoptosis in leukemic cells." Biochem.Biophy.Res.Comm.(in press.). (1998)
• [文献書誌] Terui Y.,Hatake K., et al.: "Bcl-X Is a Regulatory Factor of Apoptosis and Differentiation Megakaryocytic Lineage Cells." Exp.Hematol.(in press.). (1998)
• [文献書誌] Hatake K., et al.: "Apoptosis-gene expression in hematopoietic system:Normal and pathological conditions." Int.J.Mol.Med.1. 121-129 (1998)
• [文献書誌] Tomizuka H.,Hatake K., et al.: "CD95 predicts responsiveness to tretinoin in acute promyelocytic leukemia." Int.J.Mol.Med.1. 207-211 (1998)
• [文献書誌] Kasahara T.,Hatake K., et al.: "IL-8 and MCP-1 production by a human glioblastoma cell line,T98G in coculture with monocytes;Requirement of mococytes-associated IL-la." Eur.Cytokine.Net.(in press.). (1998)
• [文献書誌] Shimura M.,Hatake K., et al.: "Characterization of room temperature induced apoptosis in HL-60." FEBS Lett.417. 379-384 (1997)
• [文献書誌] Yamada M.,Hatake K, et al.: "Properties of murine stroma induced by M-CSF." J.Cell Physiol.173. 1-9 (1997)
• [文献書誌] Yamashita Y.,Hatake K., et al.: "Tec and JAK2 kinases cooperate to mediate cytokine-driven activation of c-fos transcription." Blood. (in press.). (1997)
• [文献書誌] Ohya K.,Hatake K., et al.: "SOCS-1/JAB/SSI-1 can bind to and suppress Tec protein-tyrosine kinase." J.Biol.Chem.272. 27178-27182 (1997)
• [文献書誌] Ohtsuki T.,Hatake K., et al.: "Expression of Src-like adapter protein mRNA is induced by all-trans retinoic acid." Biochem.Biophys.Res.Comm.230. 81-84 (1997)
• [文献書誌] Hatake,K.,et al.: "Rare but important adverse effect of all-trans retinoic acid in acute promyelocytic leukemia." Int.J.Hematol.(in press). (1997)
• [文献書誌] Ohtsuki,T.,Hatake,K.,Ikeda,M.,Temizuka,H.,Torui,Y.,Uwai,M.,Miura,Y: "Expression of Src-like adapter protein mRNA is induced by all-trans retinoic acid." Biochem.Biophys.Res.Comm.(in press). (1997)
• [文献書誌] Miyazato,A.,Yamashita,Y.,Hatake,K.,Miura,Y.,Ozawa,K.,Mano,H.: "Tec protein tyrosine kinase is involved in the signaling mec hanism of granulocyte colony-stimulating factor." Cell Growth & Differentiation.7. 1135-1139 (1996)
• [文献書誌] Izuml,T.,Ohtsuki,T.,Ohya,K-I.,Ogawa,Y.,Yoshida,M.,Muroi,K.,Imagawa,S.,Hatake,K.,Kuriki,K.,Saito,K.,Miura,Y.: "Therapy-related leukemia with a novel 21q22 rearrangement." Cancer Genet Cytogenet.90. 45-48 (1996)
• [文献書誌] Hatake,K.,Ohtsuki,T.,et al.: "Tretinoin induces bone marrow collagenous fibrosis in acute promyeiocytic leukaemia : New adverse effect but reversible." Brit.J.Haematol.93. 646-649 (1996)
• [文献書誌] Tanaka,M.,Suda,I.,Haze,K.,Nakamura,N.,Sato,K.,Kimura,F.,Motoyoshi,K.,Mizuki,M.,Tagawa,S.,et al.: "Fas ligand in human serum." Nature Medicine.2. 317-322 (1996)