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

(1).在提交的EB病毒阳性的Burkitt淋巴瘤细胞株AKATA中，功能性转化生长因子-βII型受体缺失导致对转化生长因子-β_1不敏感。转化生长因子-β-1在这些细胞系中诱导了细胞生长抑制和EB病毒的再激活，而在赤田细胞中则没有。为了阐明转化生长因子-β-1在AKATA细胞中无反应的机制，我们研究了转化生长因子-β受体和细胞内信号分子Smads的表达。所有细胞株均表达转化生长因子-βI型受体、Smad2、Smad3和Smad4。转化生长因子-βII型受体(R-II)在除AKATA细胞外的所有细胞系中均有表达。将转化生长因子-βR-II导入AKATA细胞后，对转化生长因子-β1介导的生长抑制和EB病毒的重新激活具有敏感性。为了检测转化生长因子-β受体-II基因在赤田细胞中转录抑制的可能性，组蛋白去乙酰化…的作用对更多的血管紧张素转换酶(HDAC)抑制剂曲古抑素A(TSA)进行检测。TSA诱导AKATA细胞转化生长因子-β受体-II的表达。这些结果表明，AKATA细胞中转化生长因子-β1反应的缺陷是由于缺乏转化生长因子-βR-II而引起的，而hDAC的改变可能与细胞中转化生长因子-βR-II的丢失有关。(2)经HU处理的BL细胞株Raji诱导羟基脲(HU)抗性和潜伏的EB病毒基因组丢失的机制(J.Med.Viro.70：224,2003；(3)针对p38丝裂原活化蛋白激酶或c-Myc的短干扰RNA抑制EBV阳性上皮细胞中EBV的重新激活(J.Viro.78：11798,2004)。(4)Epstein-Barr病毒在人印戒细胞胃癌细胞系HSC-39中的感染特征。(微生物与感染6：429,2004)。(5).日本慢性疲劳综合征患者中2‘，5’-寡腺苷合成酶活性和抗体的诊断评估(微生物与感染5：1096，(2003).较少

(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