Human papillomavirus 16 E5 up-regulates the expression of vascular endothelial growth factor through the activation of epidermal growth factor receptor, MEK/ERK1,2 and PI3K/Akt
Human papillomavirus 16 E5 up-regulates the expression of vascular endothelial growth factor through the activation of epidermal growth factor receptor, MEK/ERK1,2 and PI3K/Akt
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DOI：
10.1007/s00018-005-5561-x
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发表时间：
2006-04-01
影响因子：
8
通讯作者：
Song, YS
中科院分区：
文献类型：
--
作者：
Kim, SH;Juhnn, YS;Song, YS
人乳头瘤病毒（HPV）16的E5癌蛋白在早期宫颈癌发生中起重要作用。血管内皮生长因子（VEGF）在早期宫颈癌发生过程中血管生成表型的转换中起着重要作用。然而，E5和VEGF之间的关系以前没有被研究过。为了阐明E5在VEGF表达中的调节作用，我们将E5基因转入各种细胞类型。E5增加VEGF表达。表皮生长因子受体（EGFR）抑制剂的加入显着抑制VEGF的表达，表明E5通过激活EGFR刺激VEGF的表达。E5介导的EGFR活化伴随着Akt和ERK 1/2的磷酸化，它们也参与VEGF表达。此外，VEGF的mRNA稳定性不受E5的影响，但VEGF启动子活性可以通过EGFR，MEK-ERK 1/2和PI 3 K/Akt途径的抑制剂在E5表达细胞中进行调节。总的来说，这些新的结果表明HPV 16 E5通过激活EGFR、MEK/ERK 1/2和PI 3 K/Akt来增加VEGF表达。
The E5 oncoprotein of human papillomavirus (HPV) 16 plays an important role in early cervical carcinogenesis. Vascular endothelial growth factor (VEGF) plays a central role in switching on the angiogenic phenotype during early cervical carcinogenesis. However, the relationship between E5 and VEGF has not previously been examined. To clarify the regulatory role of E5 in VEGF expression, we transferred the E5 gene into various cell types. E5 increased VEGF expression. The addition of epidermal growth factor receptor (EGFR) inhibitor significantly suppressed VEGF expression, demonstrating that E5 stimulates VEGF expression through the activation of EGFR. E5-mediated EGFR activation was accompanied by phosphorylation of Akt and ERK1/2, which are also involved in VEGF expression. Furthermore, the mRNA stability of VEGF was not affected by E5, but VEGF promoter activity could be modulated by inhibitors of the EGFR, MEK-ERK1/2 and PI3K/Akt pathways in E5-expressing cells. Collectively, these novel results suggest that HPV 16 E5 increases VEGF expression by activating EGFR, MEK/ERK1/2 and PI3K/Akt.