Human T-cell leukemia virus type I Tax transactivates the matrix metalloproteinase-9 gene: potential role in mediating adult T-cell leukemia invasiveness
Human T-cell leukemia virus type I Tax transactivates the matrix metalloproteinase-9 gene: potential role in mediating adult T-cell leukemia invasiveness
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DOI：
10.1182/blood.v99.4.1341
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发表时间：
2002-02-15
期刊：
影响因子：
20.3
通讯作者：
Yamamoto, N
中科院分区：
文献类型：
--
作者：
Mori, N;Sato, H;Yamamoto, N
人类T细胞白血病病毒I型（HTLV-I）是成人T细胞白血病（ATL）和热带痉挛性下肢轻瘫/HTLV-I相关脊髓病的病原体。各种组织被循环白血病细胞浸润是ATL的特征。基质金属蛋白酶（Matrix metalloproteinases，MMPs）介导基底膜和细胞外基质的降解，在肿瘤细胞的转移和播散中起重要作用。本研究的目的是探讨是否MMP-2和MMP-9的表达失调HTLV-I感染。数据显示，与未感染的T细胞系相比，HTLV-I感染的T细胞系表达高水平的MMP-9。相比之下，HTLV-I感染并未显着改变相关MMP-2的水平。此外，MMP-9在HTLV-I感染的细胞中的表达升高归因于病毒反式激活蛋白Tax的作用。结果表明Tax可以激活MMP-9启动子并诱导T细胞中MMP-9的表达，表明MMP-9在病毒感染的细胞系中的组成型表达至少部分由Tax介导。Tax对MMP-9启动子的激活主要通过NF-κ B和SP-1的作用发生。这些观察结果的生物学意义通过以下2个发现得到验证：原代ATL细胞中MMP-9表达增加，ATL患者血浆MMP-9水平升高。此外，血浆MMP-9水平与ATL患者的器官受累相关。总之，这些数据表明，MMP-9在HTLV-1感染的细胞中的过表达可能是ATL细胞侵袭性的部分原因。(C)2002年，美国：血液学学会。
Human T-cell leukemia virus type I (HTLV-I) is the etiologic agent of adult T-cell leukemia (ATL) and of tropical spastic paraparesis/HTLV-I-associated myelopathy. Infiltration of various tissues by circulating leukemic cells is a characteristic of ATL. Matrix metalloproteinases (MMPs), which mediate the degradation of the basement membrane and extracellular matrix, play an important role in metastasis and tumor cell dissemination. The aim of this study was to explore whether expression of MMP-2 and MMP-9 was deregulated by HTLV-I infection. The data showed that HTLV-I-infected T-cell lines expressed high levels of MMP-9 compared with uninfected T-cell lines. In contrast, the levels of the related MMP-2 were not significantly altered by HTLV-I infection. In addition, the elevated expression of MMP-9 in HTLV-I-infected cells was attributable to the action of the viral transactivator protein Tax. The results show that Tax, can activate the MMP-9 promoter and induce MMP-9 expression in T cells, indicating that the constitutive expression of MMP-9 in virus-infected cell lines is at least in part mediated by Tax. Activation of, the MMP-9 promoter by Tax occurs mainly through the action of NF-kappaB and SP-1. The biologic significance of these observations was validated by the following 2 findings, MMP-9 expression was increased in primary ATL cells, and plasma MMP-9 levels were elevated in ATL patients. In addition, plasma levels of MMP-9 correlated with organ involvement in ATL patients. Together these data suggest that overexpression of MMP-9 in HTLV-I-infected cells may be In part responsible for the invasiveness of ATL cells. (C) 2002 by The American: Society of Hematology.