EBV latent membrane protein 1 activates Akt, NFkappaB, and Stat3 in B cell lymphomas.
EBV latent membrane protein 1 activates Akt, NFkappaB, and Stat3 in B cell lymphomas.
复制标题
EBV潜在膜蛋白1在B细胞淋巴瘤中激活AKT，NFKAPPAB和STAT3。
DOI：
10.1371/journal.ppat.0030166
复制
发表时间：
2007-11
期刊：
影响因子：
6.7
通讯作者：
Raab-Traub, Nancy
中科院分区：
文献类型：
--
作者：
Shair, Kathy H Y;Bendt, Katherine M;Edwards, Rachel H;Bedford, Elisabeth C;Nielsen, Judith N;Raab-Traub, Nancy
潜伏膜蛋白1（LMP 1）是EB病毒（EBV）的主要癌蛋白。在转基因小鼠中，LMP 1促进12个月龄的淋巴瘤发展增加。这项研究表明，淋巴瘤发生在B-1a淋巴细胞中，这是一个与老年小鼠转化相关的群体。淋巴瘤细胞具有失调的细胞周期标志物，并且Akt、NFκB和Stat 3的抑制剂在体外阻断LMP 1转基因淋巴细胞和淋巴瘤细胞的增强的存活力。淋巴瘤细胞的存活和增殖不依赖于IL 4/Stat 6信号传导，但具有组成性激活的Stat 3信号传导。这些相同的靶点在野生型B-1a淋巴瘤中也是失调的，这些淋巴瘤通过年龄倾向自发产生。这些结果提示Akt、NFκB和Stat 3通路可能作为治疗EBV相关B细胞淋巴瘤的有效靶点。EB病毒（EBV）与多种癌症的发生有关，包括移植后淋巴瘤、霍奇金病和鼻咽癌。潜伏膜蛋白1（LMP 1）在许多EBV相关癌症中表达，并且负责由EBV感染诱导的大多数改变的细胞生长特性。这项研究表明，LMP 1诱导B-1a淋巴细胞中的淋巴瘤，这是一种在老年小鼠中易于转化的细胞类型。淋巴瘤需要Akt、NFκB和Stat 3信号传导来增强生长和存活。Stat 3、Akt和NFκB信号通路的激活可能是LMP 1促进恶性转化能力的基础。
Latent membrane protein 1 (LMP1) is the major oncoprotein of Epstein-Barr virus (EBV). In transgenic mice, LMP1 promotes increased lymphoma development by 12 mo of age. This study reveals that lymphoma develops in B-1a lymphocytes, a population that is associated with transformation in older mice. The lymphoma cells have deregulated cell cycle markers, and inhibitors of Akt, NFκB, and Stat3 block the enhanced viability of LMP1 transgenic lymphocytes and lymphoma cells in vitro. Lymphoma cells are independent of IL4/Stat6 signaling for survival and proliferation, but have constitutively activated Stat3 signaling. These same targets are also deregulated in wild-type B-1a lymphomas that arise spontaneously through age predisposition. These results suggest that Akt, NFκB, and Stat3 pathways may serve as effective targets in the treatment of EBV-associated B cell lymphomas. Epstein-Barr virus (EBV) is linked to the development of multiple cancers, including post-transplant lymphoma, Hodgkin disease, and nasopharyngeal carcinoma. Latent membrane protein 1 (LMP1) is expressed in many EBV-associated cancers and is responsible for most of the altered cellular growth properties that are induced by EBV infection. This study reveals that LMP1 induces lymphomas in B-1a lymphocytes, a cell type that is susceptible to transformation in aged mice. The lymphomas require Akt, NFκB, and Stat3 signaling for enhanced growth and survival. The activation of the Stat3, Akt, and NFκB signaling pathways likely underlies the ability of LMP1 to promote malignant transformation.