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

机译:EBP50通过促进细胞凋亡和延迟细胞外信号调节的激酶活性发挥抑癌活性

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摘要

The expression of Ezrin-radixin-moesin-bind-ing 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 EBPSO 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 trans-fected 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.
机译:据报道,Ezrin-radixin-moesin结合磷酸蛋白50(EBP50)的表达和ebp50基因的基因内突变与人类乳腺癌的发展有关,但对乳腺癌发展及其分子机制的确切影响是尚未完全了解。在这项研究中,我们调查了EBP50在低EBPSO蛋白表达水平的乳腺癌细胞系MDA-MB-231中过表达的潜在功能。检查了EBP50过表达对细胞增殖,非锚定生长和凋亡的影响。另外,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,在稳定转染了EBP50表达质粒(EBP-231)的MDA-MB-231细胞中,细胞增殖的减少和集落形成能力的减弱是明显的。在EBP-231细胞中,自发性凋亡也有统计学上的显着增加,并伴随着ERK活性的减弱。总之,我们的结果表明,恢复EBP50的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的增殖,并且EBP50可能成为乳腺癌诊断和治疗方法的开发目标。

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