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首页> 外文期刊>Journal of Cellular Physiology >Dissecting the 17β‐estradiol pathways necessary for neuroglobin anti‐apoptotic activity in breast cancer
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Dissecting the 17β‐estradiol pathways necessary for neuroglobin anti‐apoptotic activity in breast cancer

机译：解剖17β雌二醇应承担的必要途径在乳房neuroglobin抗凋亡应承担的活动癌症

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Neuroglobin (NGB) is a relatively recent discovered monomeric heme‐protein, which behave in neurons as a sensor of injuring stimuli including oxidative stress, hypoxia, and neurotoxicity. In addition, the anti‐apoptotic activity of overexpressed NGB has been reported both in neurons and in cancer cell lines. We recently demonstrated that, NGB functions as a compensatory protein of the steroid hormone 17β‐estradiol (E2) protecting cancer cells against the apoptotic death induced by oxidative stress. However, the E2‐induced signaling pathways at the root of NGB over‐expression and mitochondrial re‐localization in breast cancer cells is still elusive. By using a kinase screening library, here, we report that: i) There is a strong positive correlation between NGB and ERα expression and activity in breast cancer cells; ii) The E2‐activated phosphatidyl‐inositol 3 kinase (PI3K)/protein kinase B (AKT) and protein kinase C (PKC) pathways are necessary to modulate the NGB protein levels; iii) The E2‐induced persistent activation of AKT drive NGB to mitochondria; iv) Reactive oxygen species (ROS)‐inducing compounds activating rapidly and transiently AKT does not affect the NGB mitochondrial level; and v) High level of NGB into mitochondria are necessary for the pro‐survival and anti‐apoptotic effect of this globin in cancer cells. As a whole, these results underline the E2 triggered pathways in E2‐responsive breast cancer cells that involve NGB as a compensatory protein devoted to cancer cell survival.
机译：Neuroglobin (NGB)是相对近期的事地理发现单体的血红素蛋白,它的行为在神经元刺激受伤的传感器包括氧化应激,缺氧,神经毒性。活动中也是NGB的报道在神经元和癌症细胞系。最近表明,NGB函数作为一个补充蛋白质的类固醇激素17β雌二醇(E2)应承担的保护癌细胞对氧化导致的凋亡的死亡压力。路径表达式和NGB的根源线粒体是定位在乳腺癌细胞仍然是难以捉摸的。筛选图书馆,在这里,我们报告:我)NGB之间有很强的正相关关系,在乳腺癌ERα表达和活动细胞;3激酶(PI3K) /蛋白激酶B(一种蛋白激酶)和蛋白激酶C (PKC)途径是必要的调节NGB蛋白水平;E2检测诱导持续激活AKT NGB开车线粒体;(ROS)迅速激活,诱导化合物瞬变AKT NGB并不影响线粒体水平;线粒体是必要的地理专业生存和抗凋亡的影响球蛋白在癌症细胞。突显出E2触发通道E2的乳腺癌细胞反应涉及NGB作为补充蛋白质致力于癌症细胞的生存。

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