Epiregulin promotes migration and invasion of salivary adenoid cystic carcinoma cell line SACC-83 through activation of ERK and Akt
Epiregulin promotes migration and invasion of salivary adenoid cystic carcinoma cell line SACC-83 through activation of ERK and Akt
复制标题
上皮调节蛋白通过激活ERK和Akt促进唾液腺腺样囊性癌细胞系SACC-83的迁移和侵袭
DOI：
10.1016/j.oraloncology.2008.04.009
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发表时间：
2009-02-01
期刊：
影响因子：
4.8
通讯作者：
Yu, Guang-yan
中科院分区：
文献类型：
--
作者：
Hu, Kai;Li, Sheng-lin;Yu, Guang-yan
血行转移是决定涎腺腺样囊性癌（SACC）预后的重要因素之一。在本研究中，我们检测了SACC细胞系中基因的表达谱，以寻找负责其独特转移特性的分子。对肺转移率低的细胞系SACC-83和肺转移率高的细胞系SACC-LM进行转录组学芯片分析，筛选出8个在SACC-LM中高表达的基因，通过实时荧光定量PCR进行验证。在这些基因中，表皮生长因子家族的新成员epiregulin在SACC-LM中的表达是SACC-83中的350倍。因此，我们也研究了表皮调节蛋白对SACC-83中迁移和侵袭的影响。作为其靶向下游分子，并发现epiregulin可以促进SACC-83的体外迁移和侵袭。此外，epiregulin不仅诱导ERK 1/2和Akt的激活，而且还诱导考克斯-2的表达。上述作用可被丝裂原活化蛋白激酶（MEK或MAPKK）特异性抑制剂U 0126或磷脂酰肌醇3-激酶（PI 3 K）特异性抑制剂LY 294002部分阻断。结论：表皮调节蛋白可能在SACC肺转移中起重要作用。(C)2008爱思唯尔有限公司保留所有权利。
Hematogenous metastasis is one of the most important factors determining the outcome of the patients with salivary adenoid cystic carcinoma (SACC). In the present study, we examined expression profile of genes in SACC cell lines to took for molecules responsible for its unique metastatic trait. A transcriptomic microarray analysis between the tower lung-metastatic rate cell line SACC-83 and the higher lung-metastatic rate cell line SACC-LM were performed, and eight genes, showed by microarray to be highly expressed in SACC-LM, were picked for validation by quantitative real-time PCR. Among the genes, the expression of epiregulin, a novel member of epidermal growth factor family, was 350-folds higher in SACC-LM than in SACC-83. Accordingly, we examined the effects of epiregulin on migration and invasion in SACC-83 as well. as its targeted downstream molecules, and found that epiregulin could promote in vitro migration and invasion in SACC-83. Furthermore, epiregulin not only induced activation of both ERK1/2 and Akt, but also expression of COX-2. In addition, all these effects could be partially blocked by U0126, a specific inhibitor of mitogen-activated protein kinase kinase (MEK or MAPKK), or LY294002, a specific inhibitor of phosphatidylinosilol 3-kinase (PI3K). Conclusively, the results suggest that epiregulin may play an important role in lung metastasis of SACC. (C) 2008 Elsevier Ltd. All rights reserved.