title: Rapid tumor formation of human T-cell leukemia virus type 1-infected cell lines in novel NOD-SCID/gammac(null) mice: suppression by an inhibitor against NF-kappaB.
abstract: We established a novel experimental model for human T-cell leukemia virus type 1 (HTLV-1)-induced tumor using NOD-SCID/gammac(null) (NOG) mice. This model is very useful for investigating the mechanism of tumorigenesis and malignant cell growth of adult T-cell leukemia (ATL)/lymphoma, which still remains unclear. Nine HTLV-1-infected cell lines were inoculated subcutaneously in the postauricular region of NOG mice. As early as 2 to 3 weeks after inoculation, seven cell lines produced a visible tumor while two transformed cell lines failed to do so. Five of seven lines produced a progressively growing large tumor with leukemic infiltration of the cells in various organs that eventually killed the animals. Leukemic cell lines formed soft tumors, whereas some transformed cell lines developed into hemorrhagic hard tumors in NOG mice. One of the leukemic cell lines, ED-40515(-), was unable to produce visible tumors in NOD-SCID mice with a common gamma-chain after 2 weeks. In vivo NF-kappaB DNA binding activity of the ED-40515(-) cell line was higher and the NF-kappaB components were changed compared to cells in vitro. Bay 11-7082, a specific and effective NF-kappaB inhibitor, prevented tumor growth at the sites of the primary region and leukemic infiltration in various organs of NOG mice. This in vivo model of ATL could provide a novel system for use in clarifying the mechanism of growth of HTLV-1-infected cells as well as for the development of new drugs against ATL.
authors.affiliation: Department of Molecular Virology, Bio-Response, Graduate School, Tokyo Medical and Dental University, Japan.
authors.forename: M Zahidunnabi
authors.initials: MZ
authors.lastname: Dewan
authors.forename: Kazuo
authors.initials: K
authors.lastname: Terashima
authors.forename: Midori
authors.initials: M
authors.lastname: Taruishi
authors.forename: Hideki
authors.initials: H
authors.lastname: Hasegawa
authors.forename: Mamoru
authors.initials: M
authors.lastname: Ito
authors.forename: Yuetsu
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Naoki
authors.initials: N
authors.lastname: Mori
authors.forename: Tetsutaro
authors.initials: T
authors.lastname: Sata
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Koyanagi
authors.forename: Michiyuki
authors.initials: M
authors.lastname: Maeda
authors.forename: Yoko
authors.initials: Y
authors.lastname: Kubuki
authors.forename: Akihiko
authors.initials: A
authors.lastname: Okayama
authors.forename: Masahiro
authors.initials: M
authors.lastname: Fujii
authors.forename: Naoki
authors.initials: N
authors.lastname: Yamamoto
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D002461:Cell Line, Transformed / Q000637:transplantation*; D004195:Disease Models, Animal; D006085:Graft Survival; D015490:HTLV-I Infections / Q000150:complications; D015368:Human T-lymphotropic virus 1 / Q000472:pathogenicity*; D006801:Humans; D015458:Leukemia, T-Cell / Q000188:drug therapy / Q000473:pathology / Q000821:virology; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000473:pathology / Q000821:virology; D008223:Lymphoma / Q000188:drug therapy / Q000473:pathology / Q000821:virology; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D009368:Neoplasm Transplantation / Q000473:pathology; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000209:etiology / Q000473:pathology; D009570:Nitriles; D009930:Organic Chemicals; D013450:Sulfones
chemical_list: C434003:3-(4-methylphenylsulfonyl)-2-propenenitrile; D000970:Antineoplastic Agents; D016328:NF-kappa B; D009570:Nitriles; D009930:Organic Chemicals; D013450:Sulfones