EBP50 inhibits EGF-induced breast cancer cell proliferation by blocking EGFR phosphorylation.
EBP50 inhibits EGF-induced breast cancer cell proliferation by blocking EGFR phosphorylation.
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EBP50 通过阻断 EGFR 磷酸化来抑制 EGF 诱导的乳腺癌细胞增殖
DOI：
10.1007/s00726-012-1277-z
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发表时间：
2012-11
期刊：
影响因子：
3.5
通讯作者：
He J
中科院分区：
文献类型：
--
作者：
Yao W;Feng D;Bian W;Yang L;Li Y;Yang Z;Xiong Y;Zheng J;Zhai R;He J
Ezrin-Radisin-Moesin结合磷蛋白-50(EBP50)抑制乳腺癌细胞的增殖，可能是通过调节表皮生长因子受体(EGFR)信号，尽管其发生的机制尚不清楚。因此，在我们的研究中，我们旨在确定EBP50的表达对EGF诱导的乳腺癌细胞株MDA-MB-231和MCF-7细胞增殖和EGFR信号激活的影响。在低水平表达EBP50的MDA-MB-231细胞中，EBP50过表达抑制了EGF诱导的细胞增殖、ERK1/2和AKT磷酸化。在高表达EBP50的MCF-7细胞中，EBP50基因敲除促进了EGF诱导的细胞增殖、ERK1/2和AKT磷酸化。EBP50基因敲除EBP50对EGF诱导的ERK1/2磷酸化的抑制作用，EBP50基因敲除的MCF-7细胞恢复EBP50对EGF诱导的ERK1/2磷酸化的抑制作用，进一步证实EBP50的表达可以特异性地抑制EGF诱导的下游分子的活化。由于EGFR信号是由EGF配体通过EGFR磷酸化而触发的，因此我们进一步检测了在EBP50表达存在或不存在的情况下EGFR的磷酸化状态。在MDA-MB-231细胞中过表达EBP50抑制了EGF刺激的EGFR磷酸化，而在MCF-7细胞中过表达EBP50则增强了EGF刺激的EGFR磷酸化。同时，在EGF刺激下，EGFR的总表达水平不受影响。综上所述，我们的数据表明EBP50可以通过抑制乳腺癌细胞中EGFR的磷酸化和阻断EGFR下游信号通路来抑制EGF诱导的乳腺癌细胞的增殖。这些结果进一步揭示了EBP50调控乳腺癌发生发展的分子机制。
Ezrin-radixin-moesin-binding phosphoprotein-50 (EBP50) suppresses breast cancer cell proliferation, potentially through its regulatory effect on epidermal growth factor receptor (EGFR) signaling, although the mechanism by which this occurs remains unknown. Thus in our studies, we aimed to determine the effect of EBP50 expression on EGF-induced cell proliferation and activation of EGFR signaling in the breast cancer cell lines, MDA-MB-231 and MCF-7. In MDA-MB-231 cells, which express low levels of EBP50, EBP50 overexpression inhibited EGF-induced cell proliferation, ERK1/2 and AKT phosphorylation. In MCF-7 cells, which express high levels of EBP50, EBP50 knockdown promoted EGF-induced cell proliferation, ERK1/2 and AKT phosphorylation. Knockdown of EBP50 in EBP50-overexpressed MDA-MB-231 cells abrogated the inhibitory effect of EBP50 on EGF-stimulated ERK1/2 phosphorylation and restoration of EBP50 expression in EBP50-knockdown MCF-7 cells rescued the inhibition of EBP50 on EGF-stimulated ERK1/2 phosphorylation, further confirming that the activation of EGF-induced downstream molecules could be specifically inhibited by EBP50 expression. Since EGFR signaling was triggered by EGF ligands via EGFR phosphorylation, we further detected the phosphorylation status of EGFR in the presence or absence of EBP50 expression. Overexpression of EBP50 in MDA-MB-231 cells inhibited EGF-stimulated EGFR phosphorylation, whereas knockdown of EBP50 in MCF-7 cells enhanced EGF-stimulated EGFR phosphorylation. Meanwhile, total expression levels of EGFR were unaffected during EGF stimulation. Taken together, our data shows that EBP50 can suppress EGF-induced proliferation of breast cancer cells by inhibiting EGFR phosphorylation and blocking EGFR downstream signaling in breast cancer cells. These results provide further insight into the molecular mechanism by which EBP50 regulates the development and progression of breast cancer.
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DOI：
10.1186/bcr737
发表时间：
2004
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
Musgrove EA
通讯作者：
Musgrove EA
影响因子：
7.4
作者：
Pan, Yong;Wang, Lei;Dai, Jiale
通讯作者：
Dai, Jiale
影响因子：
6
作者：
Fouassier, Laura;Rosenberg, Peter;Housset, Chantal
通讯作者：
Housset, Chantal
影响因子：
3
作者：
Choura, Mouna;Frikha, Fakher;Rebai, Ahmed
通讯作者：
Rebai, Ahmed
影响因子：
2.7
作者：
Fujikawa, Akihiro;Chow, Jeremy Pak Hong;Noda, Masaharu
通讯作者：
Noda, Masaharu