Study on the abnormal signal transduction of TGF-β1 in Epstein-Barr virus positive cell lines.

(1). Epstein-Barr病毒阳性的Akata Burkitt淋巴瘤细胞系缺少功能性转化生长因子(TGF)-β II型受体导致对TGF-β1不敏感（提交）。我们分析了TGF-β1对6株伯基特淋巴瘤细胞系细胞生长和eb病毒（EBV）再激活的影响。TGF-β1在这些细胞系中诱导细胞生长抑制和EBV再激活，但在Akata细胞中没有。为了阐明赤田细胞中TGF-β1无应答的机制，我们研究了TGF-β受体和细胞内信号分子Smads的表达。所有细胞系均表达TGF-β I型受体Smad2、Smad3和Smad4。TGF-β II型受体（R-II）在除Akata细胞外的所有细胞系均有表达。将TGF-β R-II引入Akata细胞可导致对TGF-β1介导的生长抑制和EBV再激活的敏感性。为了验证赤田细胞中TGF-β R-II基因转录抑制的可能性，我们研究了组蛋白去乙酰化（HDAC）抑制剂曲古抑素a （TSA）的作用。TSA诱导Akata细胞TGF-β R-II的表达。这些结果表明，赤田细胞中TGF-β1应答缺陷是由于TGF-β R-II缺乏引起的，HDAC的改变可能与细胞中TGF-β R-II的缺失有关(2)。羟基脲处理的BL细胞株对羟基脲（HU）抗性诱导机制及潜伏EBV基因组丢失[j]。70: 224, 2003; J.Med.Virol.73:589, 2004)。(3)。短干扰rna对EBV阳性上皮细胞中p38丝裂原活化蛋白激酶或c-Myc的抑制作用[j] .中华检验医学杂志，2004,(4)。eb病毒感染人胃癌印戒细胞HSC-39的研究（微生物与感染，2004）.(5)。慢性疲劳综合征患者2',5'-寡聚腺苷酸合成酶活性及抗Epatein-Barr病毒和伯纳氏柯谢氏菌抗体的诊断价值[j] .微生物与感染，（2003）。少

(1).Loss of Functional Transforming Growth Factor(TGF)-β Type II Receptor Results in Insensitivity to TGF-β1 in Epstein-Barr Virus-positive Burkitt's Lymphoma Cell Line Akata (submitted).We analyzed the effect of TGF-β1 on the cell growth and Epstein-Barr virus(EBV) reactivation in six Burkitt's lymphoma cell lines. TGF-β1 induced cell growth inhibition and EBV reactivation in these cell lines but did not in Akata cells. To elucidate the mechanism of TGF-β1 unresponsiveness in Akata cells, we studied the expression of TGF-β receptors and the intracellular signaling molecules Smads. All cell lines expressed TGF-β type I receptor, Smad2, Smad3 and Smad4. TGF-β type II receptor (R-II) was expressed in all cell lines except Akata cells. Introduction of the TGF-β R-II into Akata cells results in sensitivity to TGF-β1-mediated growth inhibition, and EBV reactivation. To test a possibility to the transcriptional repression of the TGF-β R-II gene in Akata cells, the effect of histone deacetyla … More tion (HDAC) inhibitor, trichostatin A(TSA) was examined. The expression of TGF-β R-II in Akata cells was induced by TSA treatment. These results suggest that the defect in the TGF-β1 response in Akata cells is caused by the lack of TGF-β R-II and the alteration of HDAC may be involved in the loss of TGF-β R-II in the cells.(2).Mechanism for induction of hydroxyurea(HU) resistance and loss of latent EBV genome in HU-treated BL cell line Raji (J.Med.Virol.70: 224,2003;J.Med.Virol.73:589,2004).(3).Inhibition of EBV reactivation by short interfering RNAs targeting p38 mitogen activated protein kinase or c-Myc in EBV-positive epithelial cells (J.Virol.78:11798,2004).(4).Characterization of Epstein-Barr virus infection in a human signet ring cell gastric carcinoma cell line HSC-39. (Microbes and Infection 6:429,2004).(5).Diagnostic evaluation of 2',5'-oligoadenylate synthetase activities and antibodies against Epatein-Barr virus and Coxiella burnetii in patients with choronic fatigue syndrome in Japan (Microbes and Infection 5:1096,(2003). Less