Nuclear factor-kappaB activation is involved in LMP1-mediated transformation and tumorigenesis of rat-1 fibroblasts.
Nuclear factor-kappaB activation is involved in LMP1-mediated transformation and tumorigenesis of rat-1 fibroblasts.
复制标题
DOI：
--
复制
发表时间：
2000-04
期刊：
影响因子：
11.2
通讯作者：
Zhimin He;Baozhong Xin;Xinhai Yang;Ching-ping Chan;Liang Cao
中科院分区：
文献类型：
--
作者：
Zhimin He;Baozhong Xin;Xinhai Yang;Ching-ping Chan;Liang Cao
本研究探讨了EB病毒潜伏膜蛋白LMP 1在诱导大鼠成纤维细胞转化和致瘤中的作用机制。构建了一个编码LMP 1位点特异性突变体的质粒，该突变体与肿瘤坏死因子受体相关死亡结构域蛋白结合缺陷。该LMP 1（TRADD）基因在核因子（NF）-kappaB激活中有75%缺陷，在激活蛋白-1激活中有100%缺陷。当通过逆转录病毒导入Rat-1细胞时，与Rat-1-LMP 1细胞相比，Rat-1-LMP 1（TRADD）细胞显示出病灶形成的显著减少和裸鼠中肿瘤生长的减少，这表明NF-κ B或激活蛋白-1活化对于LMP 1诱导的细胞转化可能是重要的。为了进一步描述LMP 1介导的细胞转化的决定因素，将具有显性阴性I κ B α的逆转录病毒引入转化的Rat-1-LMP 1细胞中。I κ B α的存在显著抑制了Rat-1-LMP 1细胞的病灶形成和致瘤性。我们的研究结果表明，NF-κ B的激活可能在LMP 1介导的细胞转化和肿瘤发生中发挥重要作用。
The mechanism of latent membrane protein LMP1 of EBV in inducing cell transformation and tumorigenesis was investigated in Rat-1 fibroblasts. A plasmid encoding a site-specific mutant of LMP1 defective in binding to tumor necrosis factor receptor-associated death domain protein was constructed. This LMP1(TRADD) gene is 75% defective in nuclear factor (NF)-kappaB activation and 100% defective in activator protein-1 activation. When introduced into Rat-1 cells through retrovirus, the Rat-1-LMP1(TRADD) cells showed a significant reduction of focus formation and decreased tumor growth in nude mice as compared with Rat-1-LMP1 cells, suggesting that NF-kappaB or activator protein-1 activation may be important for LMP1-induced cell transformation. To further delineate the determinants of LMP1-mediated cellular transformation, a retrovirus with a dominant-negative I kappaB alpha was introduced into the transformed Rat-1-LMP1 cells. The presence of I kappaB alpha significantly suppressed both focus formation and tumorigenicity of Rat-1-LMP1 cells. Our results suggest that the activation of NF-kappaB may play an important role in LMP1-mediated cell transformation and tumorigenesis.