The epoxyeicosatrienoic acid-stimulated phosphorylation of EGF-R involves the activation of metalloproteinases and the release of HB-EGF in cancer cells.
The epoxyeicosatrienoic acid-stimulated phosphorylation of EGF-R involves the activation of metalloproteinases and the release of HB-EGF in cancer cells.
复制标题
环氧二十碳三烯酸刺激的 EGF-R 磷酸化涉及金属蛋白酶的激活和癌细胞中 HB-EGF 的释放
DOI：
10.1038/aps.2009.184
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发表时间：
2010-02
影响因子：
8.2
通讯作者：
Wang, Dao-wen
中科院分区：
文献类型：
--
作者：
Cheng, Li-ming;Jiang, Jian-gang;Sun, Zi-yong;Chen, Chen;Dackor, Ryan T.;Zeldin, Darryl C.;Wang, Dao-wen
关键词：
目的：验证环氧二十碳三烯酸(EET)诱导的EGF-R反式激活依赖于癌细胞中金属蛋白酶的激活和随后HB-EGF的释放的假说。方法：将外源性14，15-EET分别加入4种人源性癌细胞株TCA-8113、A549、HepG2和MDA-MB-231中，或将突变的CYP环氧合酶(CYP102 F87V，一种活性的14，15-环氧合酶)导入这些细胞系。结果：在TCA-8113细胞中，加入14，15-EET和转导细胞色素P102 F87V后，EGF-R和ERK1/2酪氨酸残基的磷酸化均显著增加，该作用可被选择性EGF-R酪氨酸激酶抑制剂(Tyrphostin AG1478)、广谱金属蛋白酶抑制剂(1，10-菲咯啉)和HB-EGF释放抑制剂(CRM197)所阻断。此外，AG1478、1，10-菲咯啉和CRM197还抑制了14，15-EET诱导的A549、HepG2和MDA-MB-231细胞中EGF-R和ERK1/2的酪氨酸磷酸化。结论：EET诱导的EGF-R的反式激活依赖于金属蛋白酶的激活和随后HB-EGF的释放。
Aim:To test the hypothesis that the epoxyeicosatrienoic acid (EET)-induced transactivation of EGF-R depends on the activation of metalloproteinases and the subsequent release of HB-EGF in cancer cells.Methods:Exogenous 14, 15-EET were added to four human-derived cancer cell lines Tca-8113, A549, HepG2, and MDA-MB-231, or these same cell lines were transfected with a mutant CYP epoxygenase (CYP102 F87V, an active 14, 15-epoxygenase). The effects of elevated EET levels on the phosphorylation of tyrosine residues in the EGF receptor and on ERK1/2 activation were then assessed.Results:Both the addition of 14, 15-EET and the transfection of cells with CYP102 F87V markedly increased the phosphorylation of the tyrosine residues of EGF-R and ERK1/2, an effect that was blocked by a selective EGF-R tyrosine kinase inhibitor (tyrphostin AG1478), a broad-spectrum metalloproteinase inhibitor (1, 10-phenanthroline), and an inhibitor of HB-EGF release (CRM197) in Tca-8113 cells. In addition, AG1478, 1, 10-phenanthroline, and CRM197 also inhibited the tyrosine phosphorylation of EGF-R and ERK1/2 that was induced by 14, 15-EET in the A549, HepG2, and MDA-MB-231 cell lines.Conclusion:These results suggest that the EET-induced transactivation of EGF-R depends on activation of metalloproteinases and the subsequent release of HB-EGF in cancer cell lines.
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影响因子：
11.2
作者：
Miyamoto, S;Hirata, M;Mekada, E
通讯作者：
Mekada, E
影响因子：
13.6
作者：
Chen, Jianchun;Chen, Jian-Kang;Harris, Raymond C.
通讯作者：
Harris, Raymond C.
影响因子：
5.4
作者：
Xiao, XA;Li, JA;Samulski, RJ
通讯作者：
Samulski, RJ
影响因子：
11.4
作者：
Izumi, Y;Hirata, M;Mekada, E
通讯作者：
Mekada, E
影响因子：
4.8
作者：
Gechtman, Z;Alonso, JL;Klagsbrun, M
通讯作者：
Klagsbrun, M