Epstein-Barr virus-encoded small RNA induces insulin-like growth factor 1 and supports growth of nasopharyngeal carcinoma-derived cell lines
Epstein-Barr virus-encoded small RNA induces insulin-like growth factor 1 and supports growth of nasopharyngeal carcinoma-derived cell lines
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DOI：
10.1038/sj.onc.1208357
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发表时间：
2005-03-03
期刊：
影响因子：
8
通讯作者：
Takada, K
中科院分区：
文献类型：
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作者：
Iwakiri, D;Sheen, TS;Takada, K
为探讨胰岛素样生长因子1（IGF-1）在鼻咽癌（NPC）生长中的作用，本研究检测了三种NPC细胞系C666-1、CNE-1和HONE-1。C666-1细胞保持Epstein-Barr病毒（EBV）表达的NPC表型，并且对IGF-1分泌呈阳性，并且在低血清条件下用抗IGF-1抗体处理它们的生长被显著抑制。另一方面，CNE 1和HONE 1细胞是EBV阴性的，并且不分泌IGF-1。虽然它们在低血清条件下不能生长，但添加重组IGF-1使它们生长。CNE 1和HONE 1细胞的EBV转化再现了EBV表达并伴随IGF-1表达的NPC表型。虽然它们可以在低血清条件下生长，但它们的生长被抗IGF-1抗体处理显著抑制。这些结果表明，EBV感染诱导NPC细胞系中的IGF-1，分泌的IGF-1作为自分泌生长因子。这些发现似乎在体内是有效的，因为NPC活检始终表达IGF-1。进一步的研究表明，IGF-1表达的增加反映了转录激活，EBV编码的小RNA（EBER）负责IGF-1的诱导。EBER总是在EBV相关的恶性肿瘤中表达，包括NPC。本研究结果有力地表明，EBER直接影响NPC的发病机制。
To assess the role of insulin-like growth factor 1 (IGF-1) in the growth of nasopharyngeal carcinoma (NPC), three NPC-derived cell lines, C666-1, CNE1 and HONE1, were examined. C666-1 cells maintained NPC phenotype of Epstein-Barr virus (EBV) expression and were positive for IGF-1 secretion, and their growth was strikingly inhibited by treatment with an anti-IGF-1 antibody under low serum condition. On the other hand, CNE1 and HONE1 cells were EBV-negative and did not secrete IGF-1. Although they could not grow under low serum condition, addition of recombinant IGF-1 made them grow. EBV conversion of CNE1 and HONE1 cells reproduced NPC phenotype of EBV expression and accompanied IGF-1 expression. Although they could grow under low serum condition, their growth was strikingly inhibited by treatment with the anti-IGF-1 antibody. These results suggest that EBV infection induces IGF-1 in NPC cell lines, and that the secreted IGF-1 acts as an autocrine growth factor. These findings seem to be operative in vivo, as NPC biopsies consistently express IGF-1. Further studies demonstrated that increased IGF-1 expression reflected transcriptional activation, and EBV-encoded small RNA ( EBER) was responsible for IGF-1 induction. EBER is invariably expressed in EBV-associated malignancies, including NPC. The present findings strongly suggest that EBER directly affects the pathogenesis of NPC.