Induction of c-Met proto-oncogene by Epstein-Barr virus latent membrane protein-1 and the correlation with cervical lymph node metastasis of nasopharyngeal carcinoma
Induction of c-Met proto-oncogene by Epstein-Barr virus latent membrane protein-1 and the correlation with cervical lymph node metastasis of nasopharyngeal carcinoma
复制标题
DOI：
10.1016/s0002-9440(10)61669-0
复制
发表时间：
2001-07-01
影响因子：
6
通讯作者：
Yoshizaki, T
中科院分区：
文献类型：
--
作者：
Horikawa, T;Sheen, TS;Yoshizaki, T
鼻咽癌（Nasopharyngealcarcinoma，NPC）是头颈部肿瘤中最独特的一种，它与EB病毒（Epstein-Barr virus，EB病毒）密切相关，且具有高度转移性。细胞运动性的上调对于增强转移潜能是必需的。c-Met原癌基因是肝细胞生长因子/散射因子的高亲和力受体，其表达与肿瘤细胞的转移能力有关，我们观察到c-Met表达与颈淋巴结转移密切相关（P = 0.0272）在39例鼻咽癌标本中，EB病毒编码的潜伏膜蛋白-1（LMP-1）是一种主要的癌基因，并被认为增强NPC的转移特性。我们报道了LMP-1增强Madin-Darby犬肾（MDCK）上皮细胞的运动性，这是通过激活Ets-1转录因子介导的。因此，我们研究了LMP-1，Ets-1和c-Met的相互关系。LMP-1、Ets-1和c-Met在鼻咽癌组织中的表达存在显著相关性（LMP-1 vs Ets-1，P < 0.0001; Ets-1 vs c-Met，P = 0.0012; LMP-1 vs Met，P <0.0005）。转染MDCK细胞的LMP-1表达质粒可诱导c-Met蛋白的表达，Ets-1的表达也可诱导c-Met蛋白的表达，而在表达LMP-1的MDCK细胞中引入显性阴性形式的Ets-1可抑制LMP-1对c-Met的诱导。这些结果表明，LMP-1通过激活Ets-1诱导c-Met，这可能部分有助于NPC的高转移潜力。
Nasopharyngeal carcinoma (NPC) is distinctive in head and neck carcinomas for its close association with Epstein-Barr virus and Its highly metastatic nature. Up-regulation of cell motility Is essential for enhancement of metastatic potential. The expression of c-Met proto-oncogene, a high-affinity receptor for hepatocyte growth factor/scatter factor, has been reported to correlate with metastatic ability of the tumor cell We observed close association of c-Met expression with cervical lymph node metastasis (P = 0.0272) In 39 NPC specimens studied immunohistochemically, Epstein-Barr virus-encoding latent membrane protein-1 (LMP-1) is a primary oncogene and is suggested to enhance the metastatic property of NPC, Previously, we reported that LMP-1 enhanced the motility of Madin-Darby canine kidney (MDCK) epithelial cells that was mediated by activation of Ets-1 transcription factor. Therefore, we examined the interrelationships of LMP-1, Ets-1, and c-Met. In immunohistochemical studies, the expression of LMP-1, Ets-1, and c-Met correlated significantly with each other in NPC (LMP-1 versus Ets-1, P < 0.0001; Ets-1 versus c-Met, P = 0.0012; LMP-1 versus Met, P 0.0005). Transfection of LMP-1-expressing plasmid in MDCK cells induced c-Met protein expression, The c-Met protein was also induced by Ets-1 expression, and induction of c-Met by LMP-1 was suppressed by introducing a dominant-negative form of Ets-1 in LMP-1-expressing MDCK cells. These results suggest that LMP-1 induces c-Met through the activation of Ets-1, which may contribute in part to the highly metastatic potential of NPC.