EBP50 exerts tumor suppressor activity by promoting cell apoptosis and retarding extracellular signal-regulated kinase activity

EBP50 exerts tumor suppressor activity by promoting cell apoptosis and retarding extracellular signal-regulated kinase activity
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EBP50 通过促进细胞凋亡和延缓细胞外信号调节激酶活性发挥肿瘤抑制活性

DOI:
10.1007/s00726-009-0437-2
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发表时间:
2010-04-01
期刊:
影响因子:
3.5
通讯作者:
He, Junqi
He, Junqi
中科院分区:
生物学3区
文献类型:
--
作者:
Zheng, Jun-Fang;Sun, Li-Cui;He, Junqi

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Ezrin-radixin-moesin-binding phosphoprotein-50(EBP 50)基因的表达和基因内突变与乳腺癌的发生有关,但其确切的影响及其分子机制尚不清楚。在这项研究中,我们研究了EBP 50通过在乳腺癌细胞系MDA-MB-231中过表达的潜在功能,该细胞系具有低EBP 50蛋白表达水平。检测EBP 50过表达对细胞增殖、非贴壁依赖性生长和凋亡的影响。此外,还测定了细胞外信号调节激酶(ERK)的活性。我们的结果表明,与对照细胞相比,在稳定转染EBP 50表达质粒(EBP-231)的MDA-MB-231细胞中,细胞增殖和集落形成能力明显下降。在EBP-231细胞中自发凋亡也有统计学显著增加,伴随着ERK活性的减弱。总之,我们的研究结果表明,恢复EBP 50表达可以通过促进细胞凋亡和抑制ERK活性来抑制乳腺癌细胞增殖,EBP 50可能是乳腺癌诊断和治疗的发展目标。
The expression of Ezrin-radixin-moesin-binding phosphoprotein-50 (EBP50) and the intragenic mutation of the ebp50 gene have been reported to correlate with human breast cancer development, but the exact impacts on breast cancer development and its molecular mechanism are not fully understood. In this study, we investigate the potential function of EBP50 through over-expression in the breast cancer cell line, MDA-MB-231, which has low EBP50 protein expression levels. The effects of EBP50 over-expression on cellular proliferation, anchorage-independent growth and apoptosis were examined. In addition, the activity of extracellular signal-regulated kinase (ERK) was also determined. Our results show that a decrease of cellular proliferation and attenuation of colony-forming ability were evident in MDA-MB-231 cells stably transfected with an EBP50 expressing plasmid (EBP-231) when compared with control cells. There was also a statistically significant increase in spontaneous apoptosis in EBP-231 cells accompanied by an attenuation in ERK activity. Altogether, our results suggest that restoring EBP50 expression could suppress breast cancer cell proliferation by promoting cell apoptosis and inhibiting ERK activity, and that EBP50 may be a target for development of diagnostics and therapeutics in breast cancer.