The contribution of NF-κB activity to spontaneous proliferation and resistance to apoptosis in human T-cell leukemia virus type 1 Tax-induced tumors
The contribution of NF-κB activity to spontaneous proliferation and resistance to apoptosis in human T-cell leukemia virus type 1 Tax-induced tumors
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DOI：
10.1182/blood.v98.4.1200
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发表时间：
2001-08-15
期刊：
影响因子：
20.3
通讯作者：
Ratner, L
中科院分区：
文献类型：
--
作者：
Portis, T;Harding, JC;Ratner, L
人T细胞白血病病毒I型是成人T细胞白血病/淋巴瘤的病原体。这种病毒的Tax蛋白被认为有助于细胞转化和肿瘤发展。在这份报告中，我们已经使用了税收转基因小鼠模型的肿瘤发生的核因子（NF）-κ B活性的贡献，自发肿瘤细胞增殖和抗凋亡。我们已经证明，在Tax转基因小鼠新鲜分离的原发性肿瘤中，NF-κ B诱导的细胞因子（包括白细胞介素（IL）-6，IL-10，IL-15和干扰素（IFN）-γ）的表达水平升高。NF-κ B活性抑制剂水杨酸钠和环戊烯酮前列腺素（前列腺素A（1）和15-脱氧-δ（12，14）前列腺素J（2））阻断Tax转基因小鼠脾细胞的自发增殖。此外，Tax诱导的肿瘤细胞对辐射诱导的凋亡具有抗性，在水杨酸钠和洋地黄素的存在下，Tax诱导的肿瘤细胞变得对凋亡敏感。这些结果强烈表明，Tax介导的NF-κ B活性诱导有助于体内肿瘤发生。
Human T-cell leukemia virus type I is the etiologic agent of adult T-cell leukemia/ lymphoma. The Tax protein of this virus is thought to contribute to cellular transformation and tumor development. In this report, we have used a Tax transgenic mouse model of tumorigenesis to study the contribution of nuclear factor (NF)-kappaB activity to spontaneous tumor cell proliferation and resistance to apoptosis. We have demonstrated elevated expression levels of NF-kappaB-inducible cytokines, including interleukin (IL)-6, IL-10, IL-15, and interferon (IFN)-gamma, in freshly isolated primary tumors from Tax transgenic mice. Inhibitors of NF-kappaB activity, sodium salicylate and cyclopentenone prostaglandins (prostaglandin A(1) and 15-deoxy-Delta (12,14)prostaglandin J(2)), blocked spontaneous proliferation of Tax transgenic mouse spleen cells. In addition, Tax-induced tumor cells, which are resistant to irradiation-induced apoptosis, became sensitive to apoptosis in the presence of sodium salicylate and prostaglandins. These results strongly suggest that Tax-mediated induction of NF-kappaB activity contributes to tumorigenesis in vivo.