1995 年度実績報告書

HTLV-1による細胞がん化の分子構造

研究課題

研究課題/領域番号	06280103
研究機関	東北大学
研究代表者	菅村和夫東北大学, 医学部, 教授 (20117360)
研究分担者	吉木敬北海道大学, 医学部, 教授 (60220612) 内山卓京都大学, ウイルス研究所, 教授 (80151900) 藤沢順一関西医科大学, 教授 (40181341) 赤城剛国立がんセンター研究所, ウイルス部, 研究員 (90184077) 藤井雅寛東京医科歯科大学, 助教授 (30183099)
キーワード	HTLV-I / 成人T細胞白血病 / HAM / 転写活性化因子 / トランスフォーメイション
研究概要	Taxの転写活性化の新たな標的としてTNF受容体ファミリーのOX40が同定され、HTLV-I感染T細胞におけるOX40/OX40リガンド(gp34)系を介した増殖刺激作用の存在が示唆された。HTLV-Iエンハンサーには種々のAP-1蛋白が結合し、Tax非依存性ウイルス遺伝子発現に関わっていることが示唆された。HTLV-I・taxによるラット線維芽細胞のトランスフォーメーションにTaxのCArGボックス活性化あるいはNF-kB活性化能が関与していることが示された。細胞周期制御因子の中で、Tax発現細胞において特異的に発現増強される因子と発現低下する因子とが存在することが示された。新鮮ATL細胞やATL由来細胞株がSCIDマウスに対して高い造腫瘍性を示したが、ATL非由来HTLV-I感染細胞株造腫瘍性はみられなかった。HTLV-Iによる各種疾患の発症モデル動物として作製されたpX遺伝子トランスジェニックラット、env-pXトランスジェニックラットの病態解析から、pX遺伝子トランスジェニックラットではTax高発現の原発性乳ガンがみとめられ、env-pXトランスジェニックラットではcollagen vascular diseasesの発症がみられた。

研究成果
(17件)

すべてその他

すべて文献書誌 (17件)

[文献書誌] Ohbo,K: "Functional analysis of the human interleukin 2 receptor γ chain gene promoter." J.Biol.Chem. 13. 7479-7486 (1995)
[文献書誌] Ohbo,K: "Modulation of hematopoiesis in mouse with a truncated mutant of the interleukin-2 receptor γ chain." Blood. (in press).
[文献書誌] Higashimura,N.: "Indution of OX40,a receptor of gp34,on T cells by Trans-acting transcriptional activator,Tax,of human T-cell leukemia virus type I." Jpn.J.Caner Res.(in press).
[文献書誌] Fujii,M: "c-Jun,c-Fos and their family members activate the transcription mediated by three 21bp repetitive sequences in the HTLV-I long terminal repeat." Intervirol.(in press).
[文献書誌] Fujii,M: "Identification of the Tax interactuion region of serum response factor that mediates the abberant induction of imediate early genes through CArG boxes by HTLV-I Tax." Oncogene. 11. 7-14 (1995)
[文献書誌] Matsuzaki,Y.: "Identification of transcriptional activation domain of TREB3,a CREB/ATF family protein that binds to HTLV-I enhancer." J.Biochem.117. 303-308 (1995)
[文献書誌] Murakami,T.: "HTLV-I tax enhancer NF-Kapper-B2 expression and binds to the products p52 and p100,but does not suppress the inhibitory function of p100." Virology. 206. 1066-1074 (1995)
[文献書誌] Yamaoka,S.: "Constitutive activation of NF-kB is essential for transformation of rat fibroblasts by the human T-cell leukemia virus tyoe I Tax protein." EMBOJ.(in press).
[文献書誌] Akagi,T.: "Characterization of T-cells immortalized by Tax of human T-cell leukemia virus type 1." Blood. 87(in press).
[文献書誌] Akagi,T,: "Increased Protein tyrosine-Phosphorylation in primary T-cells transformed with Tax1 of human T-cell leukemia virus Type I." FEBS Lett.358. 34-38 (1995)
[文献書誌] Imada,K.: "Tumorigenicity of human T-cell leukemia virus type I-infected cell lines in severe combined immunodeficient mice and characterization of the cells proliferating in vivo." Blood. 86. 2350-2357 (1995)
[文献書誌] Uchiyama,T.: "Adhesion properties of adult T cell leukemia cells." Leukemia and Lymphoma. 16. 407-412 (1995)
[文献書誌] Takaori-Kondo.A.: "Detection of homing,proliferation,and infiltration sites of adult T cell leukemia cells in severe combined immunodeficiency mice using radiometric techniques." Jpn.J.Cancer Res.86. 322-328 (1995)
[文献書誌] Hosono,M.: "Radioimmunodetection of human leukemia with anti-interleukin-2 receptor antibody in severe combined immunodeficiency mice." Nuclear medicine and Biology. 22. 869-874 (1995)
[文献書誌] Seto,K.: "A ral model of HTLV-I intection.Development of chronic progressive myelopathy in seropositive WKAH rats and related apotosis." Acta Neuropathl.89. 483-490 (1995)
[文献書誌] Yamada,S.: "Cytokine-producing mammary carcinomas in transgenic rats carrying the pX gene of human T-lymphotropic virus type I." Cancer Res.55. 2524-2527 (1995)
[文献書誌] Takeuchi,K.: "Expression of endogenous retroviruses,ERV3 and λ4-1,in synovial tissues from patients with rheumatoid arthritis." Clin.Exp.Immunol.99. 338-344 (1995)

1995 年度 実績報告書

HTLV-1による細胞がん化の分子構造

研究代表者

菅村 和夫 東北大学, 医学部, 教授 (20117360)

研究成果

[文献書誌] Ohbo,K: "Functional analysis of the human interleukin 2 receptor γ chain gene promoter." J.Biol.Chem. 13. 7479-7486 (1995)

[文献書誌] Ohbo,K: "Modulation of hematopoiesis in mouse with a truncated mutant of the interleukin-2 receptor γ chain." Blood. (in press).

[文献書誌] Higashimura,N.: "Indution of OX40,a receptor of gp34,on T cells by Trans-acting transcriptional activator,Tax,of human T-cell leukemia virus type I." Jpn.J.Caner Res.(in press).

[文献書誌] Fujii,M: "c-Jun,c-Fos and their family members activate the transcription mediated by three 21bp repetitive sequences in the HTLV-I long terminal repeat." Intervirol.(in press).

[文献書誌] Fujii,M: "Identification of the Tax interactuion region of serum response factor that mediates the abberant induction of imediate early genes through CArG boxes by HTLV-I Tax." Oncogene. 11. 7-14 (1995)

[文献書誌] Matsuzaki,Y.: "Identification of transcriptional activation domain of TREB3,a CREB/ATF family protein that binds to HTLV-I enhancer." J.Biochem.117. 303-308 (1995)

[文献書誌] Murakami,T.: "HTLV-I tax enhancer NF-Kapper-B2 expression and binds to the products p52 and p100,but does not suppress the inhibitory function of p100." Virology. 206. 1066-1074 (1995)

[文献書誌] Yamaoka,S.: "Constitutive activation of NF-kB is essential for transformation of rat fibroblasts by the human T-cell leukemia virus tyoe I Tax protein." EMBOJ.(in press).

[文献書誌] Akagi,T.: "Characterization of T-cells immortalized by Tax of human T-cell leukemia virus type 1." Blood. 87(in press).

[文献書誌] Akagi,T,: "Increased Protein tyrosine-Phosphorylation in primary T-cells transformed with Tax1 of human T-cell leukemia virus Type I." FEBS Lett.358. 34-38 (1995)

[文献書誌] Imada,K.: "Tumorigenicity of human T-cell leukemia virus type I-infected cell lines in severe combined immunodeficient mice and characterization of the cells proliferating in vivo." Blood. 86. 2350-2357 (1995)

[文献書誌] Uchiyama,T.: "Adhesion properties of adult T cell leukemia cells." Leukemia and Lymphoma. 16. 407-412 (1995)

[文献書誌] Takaori-Kondo.A.: "Detection of homing,proliferation,and infiltration sites of adult T cell leukemia cells in severe combined immunodeficiency mice using radiometric techniques." Jpn.J.Cancer Res.86. 322-328 (1995)

[文献書誌] Hosono,M.: "Radioimmunodetection of human leukemia with anti-interleukin-2 receptor antibody in severe combined immunodeficiency mice." Nuclear medicine and Biology. 22. 869-874 (1995)

[文献書誌] Seto,K.: "A ral model of HTLV-I intection.Development of chronic progressive myelopathy in seropositive WKAH rats and related apotosis." Acta Neuropathl.89. 483-490 (1995)

[文献書誌] Yamada,S.: "Cytokine-producing mammary carcinomas in transgenic rats carrying the pX gene of human T-lymphotropic virus type I." Cancer Res.55. 2524-2527 (1995)

[文献書誌] Takeuchi,K.: "Expression of endogenous retroviruses,ERV3 and λ4-1,in synovial tissues from patients with rheumatoid arthritis." Clin.Exp.Immunol.99. 338-344 (1995)

1995 年度実績報告書

菅村和夫東北大学, 医学部, 教授 (20117360)