EBウイルスとヒト発がん

1999 Fiscal Year Annual Research Report

• Project/Area Number: 09253103
• Research Institution: Tottori University
• Principal Investigator: 西連寺 剛 鳥取大学, 医学部, 教授 (10117351)
• Co-Investigator(Kenkyū-buntansha): 青笹 克之 大阪大学, 医学部, 教授 (30115985) ; 榮鶴 義人 鹿児島大学, 医学部, 教授 (00041351) ; 平井 莞二 東京医科歯科大学, 難治疾患研究所, 教授 (00100991) ; 柿井 秀雄 山口大学, 医学部, 講師 (60220175) ; 深山 正久 東京大学, 医学部, 教授 (70281293)
• Keywords: EBウイルス(EBV) / EBV関連胃癌 / EBV関連悪性リンパ腫 / EBV発がん / EBV感染細胞株 / NKリンパ腫 / EBNA-LP / アポトーシス

Research Abstract

1.EBV関連胃癌(以下EBV胃癌と略)は極く早期段階からmonoclonalで、多発癌の頻度が高く随伴癌の多くはEBV感染癌であることを明らかにした。
2.EBV胃癌が萎縮性胃炎の先端部に発生し、腺管改築の場である胃粘膜萎縮境界と密接に関連した癌であることを明らかにした。
3.EBVが一部の胃癌細胞にのみ感染した癌を見出し、その癌部及び非癌部から性状の異なる2つのEBV感染細胞株を樹立した。
4.nasalT/NK-cell lymphoma(NTL)は、NK細胞由来でありEBVゲノムの発現は潜伏感染2型であった。
5.EBV陽性進行性鼻壊疸の腫瘍細胞株の樹立に成功し、NK及びγδT細胞由来を証明し、NK株の全てに6番染色体異常を認めた。
6.EBV感染膿胸関連リンパ腫(PAL)と鼻腔NK細胞リンパ腫(NNKCL)のcytotoxic T-cell(CTL)の免疫監視の逸脱機構に相違を見出した。
7.EBNA-LPの細胞質での発現、細胞制御因子HAX-1と共局在し、EBNA-LPのホモダイマーの形成を明らかにした。
8.アポトーシス制御EBV蛋白質LMP1はC末端領域が活性発現に重要であり、BHRF1はTRAILによるアポトーシスを制御し、caspase-8の活性化を阻害することを明らかにした。

Research Products

• [Publications] Gao,X. et al.: "Nitric oxide down-regulates Epstein-Barr virus reactivation in epithelial cell lines"Virology. 258. 375-381 (1999)
• [Publications] Sairenji,T.: "Epstein-Barr virus(EBV) infection and gastric carcinoma:The approach through EBV infected epithelial cell lines"Jpn.J.Infect.Dis.. 52. 110-112 (1999)
• [Publications] Izawa,N. et al: "Identification of an alternative form of caspase-9 in human gastric cancer cell lines : a role of p caspase 9 variant in apoptosis resistance"Apoptosis. 4. 321-325 (1999)
• [Publications] Kanamori et al.: "Differential effects of TPA ** cell growth and Epstein-Barr virus reactivation in epithelial cell lined derived from gastric tissues and B cell line Raji"Virus Genes. 20. 113-121 (2000)
• [Publications] Ikuta et al.: "Defection of Epstein-Barr virus in salivas and throat washings in healthy adults and children"Microbes and Infection. 2. 1-6 (2000)
• [Publications] Fukada et al.: "Inhibition of cell growth and Epstein-Barr virus(EBV) reactivation by CD 40 stimulation in EBV-transformed B cell"Viral Immunol.. (in press). (2000)
• [Publications] Takanashi,M.,et al.: "Tumorigenicity of mouse BALB/c3T3 fibroblast cells witch express Epstein-Barr viruse ncoded LMPI and show normal growth phenotypes in vitro is correlated with loss of transforming growth factor-I:mediated growth inhibition"Arch.Virol.. 144. 241-257 (1999)
• [Publications] Kawaguchi,K.,et al.: "The cellular elongation factoe I is modified in cells infected with representative alpha-,beta-,or gamma-herpesviruses"J.Virol.. 73. 4456-4460 (1999)
• [Publications] Tanaka,M.,et al.: "Sequence variations of Epstein-Barr virus LMP2A gene in gastric carcinoma in Japan"Virus Genes. 19. 103-111 (1999)
• [Publications] Shirakata,M.et al.: "Requirement of cellular licensing process for the dyad symmetry region:dependent replication of the EBV or iP minichromosome"Virology. 263. 42-54 (1999)
• [Publications] Yamamoto,T.,et al.: "Epstein-Barr virus(EBV) infected cells were frequently but dispersely detected in T-cell lymphomas of various types by insitu hybridization with a RNA probe specific to EBV specific nuclear antigen 1"Virus Res.. (in press). (2000)
• [Publications] Ikeda,T.,et al.: "Defection of lymphocytes productively infected with Epstein-Barr virus in non-neoplastic tonsils"J.gon.Virol.. (in press). (2000)
• [Publications] Mori,S,et al: "Deletions and Single-basemutations within the oarboxy-terminal region of the latent membrane protein1 encogene in Epstein-Barr virus related gastric cancer of southern Japan"J.Med.Virol.. 57. 152-158 (1999)
• [Publications] Herrera.Goepfert,R. et al.: "Epsttein-Barr virus associated gastric carcinoma in Mexico.Analysis of 135 consecutive gastrectomies in two hospitals"Modern Pathol.. 12. 873-878 (199)
• [Publications] Shinkura,R.et al.: "Epstein-Barr virus specific antibodies in EBV-positive and negative gastric carcinoma cases in Japan"J.Med.Virol.. (in press). (2000)
• [Publications] Ohsawa,M.et al.: "Immunophenotypic and genotypic characterization of nasal lymphoma with polymorphic reticulosismorphology"Int.J.cancer. 81. 865-870 (1999)
• [Publications] Kanno,H.et al.: "HLA-A alleles of patients with pyothorax associated lymphoma:Delineation of anti-Epstein-Barr virus(EBV) host immune response during the development of EBV patent antigen poritive lymphomas"Int.J.cancer. 82. 630-634 (1999)
• [Publications] Takakuwa,T.et al.: "No evidence of replication error phenotype in nasal NK/T cell lymphoma"Int.J.cancer. 84. 623 (1999)
• [Publications] Miwa,H,et al.: "Pyruvate secreted by human lymphoid cell lines protects cells from hydrogen peroxide mediated apoptosis"Fres Rad.Res.. (in press). (2000)
• [Publications] Kanno,H.et al.: "Low frequency of HLA-AO201 allele in patients with Epstein-Barr virus positive nasal lymphomas with polymorphic reticulosis morphology"Int.J.cancer. (in press). (2000)
• [Publications] Li,T.,et al.: "Mutations of p53 geno in nasal NK/T cell lymphoma"Lad Invest. (in press). (2000)
• [Publications] Kaizaki,Y.,et al.: "Atrophic gastritis Epstein-Barr virus infection, and Wpstein-Barr virus-associated gastric carcinoma"gastric Cancer. 2. 101-108 (1999)
• [Publications] Yanai,H.,et al.: "Epstein-Barr virus infection of the colon with inflammatory bowel desease"Am.J.Gastrienterol. 94. 1582-1586 (1999)
• [Publications] Yanai,H.,et al.: "Epstein-Barr virus-associated gastric carcinoma and atrophic gastritis"J.clinic.Gastroenterrol. 29. 39-43 (1999)
• [Publications] Kawanishi,M.: "The Epstein-Barr virus latent membrane proteinI(LMPI) enhances TNF alpha-induced apoptosis of intestine 407 epithelial cells : the role of LMPI terminal activation regions land2"Virology. (in press). (2000)