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ELK3 Expression Correlates With Cell Migration, Invasion, and Membrane Type 1-Matrix Metalloproteinase Expression in MDA-MB-231 Breast Cancer Cells

机译:ELK3表达与MDA-MB-231乳腺癌细胞中的细胞迁移,侵袭和膜1-基质金属蛋白酶表达相关。

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摘要

ELK3 is a member of the Ets family of transcription factors. Its expression is associated with angiogenesis, vasculogenesis, and chondrogenesis. ELK3 inhibits endothelial migration and tube formation through the regulation of MT1-MMP transcription. This study assessed the function of ELK3 in breast cancer (BC) cells by comparing its expression between basal and luminal cells in silico and in vitro. In silico analysis showed that ELK3 expression was higher in the more aggressive basal BC cells than in luminal BC cells. Similarly, in vitro analysis showed that ELK3 mRNA and protein expression was higher in basal BC cells than in normal cells and luminal BC cells. To investigate whether ELK3 regulates basal cell migration or invasion, knockdown was achieved by siRNA in the basal BC cell line MDA-MB-231. Inhibition of ELK3 expression decreased cell migration and invasion and downregulated MT1-MMP, the expression of which is positively correlated with tumor cell invasion. In silico analysis revealed that ELK3 expression was associated with that of MT1-MMP in several BC cell lines (0.98 Pearson correlation coefficient). Though MT1-MMP expression was upregulated upon ELK3 nuclear translocation, ELK3 did not directly bind to the 1.3-kb promoter region of the MT1-MMP gene. These results suggest that ELK3 plays a positive role in the metastasis of BC cells by indirectly regulating MT1-MMP expression.
机译:ELK3是Ets转录因子家族的成员。它的表达与血管生成,血管生成和软骨形成有关。 ELK3通过调节MT1-MMP转录抑制内皮迁移和管形成。这项研究通过比较硅胶和体外基底细胞和腔细胞之间的表达,评估了ELK3在乳腺癌(BC)细胞中的功能。在计算机分析中显示,在更具侵略性的基础BC细胞中,ELK3表达高于在管腔BC细胞中。同样,体外分析表明,基底BC细胞中ELK3 mRNA和蛋白表达高于正常细胞和管腔BC细胞。为了研究ELK3是否调节基底细胞迁移或侵袭,通过siRNA在基底BC细胞系MDA-MB-231中实现了敲低。抑制ELK3表达可降低细胞迁移和侵袭并下调MT1-MMP,其表达与肿瘤细胞侵袭呈正相关。在计算机分析中,ELK3的表达与几种BC细胞系中MT1-MMP的表达相关(Pearson相关系数为0.98)。尽管ELK3核易位时MT1-MMP表达上调,但ELK3并不直接结合MT1-MMP基因的1.3-kb启动子区域。这些结果表明,ELK3通过间接调节MT1-MMP表达在BC细胞转移中发挥积极作用。

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