p21蛋白激活激酶4在乳腺癌上皮间质转化中的作用研究

发布时间：2018-12-20 19:03

【摘要】：目的:探讨p21蛋白激活激酶4(PAK4)在乳腺癌细胞上皮间质转化中的作用。方法:在乳腺癌MCF7细胞中超表达PAK4,而在乳腺癌MDA-MB-231细胞中干扰PAK4表达,通过迁移和侵袭实验检测其对乳腺癌细胞迁移侵袭的影响,荧光定量法和免疫印迹分析检测PAK4、E-Cadherin、N-Cadherin、Vimentin mRNA和蛋白质表达量变化,免疫印迹法检测EMT相关转录激活因子Snail、Slug表达量变化。结果:MCF7细胞超表达PAK4后,细胞的迁移侵袭能力显著增加,并且上皮标志分子E-Cadherin蛋白表达下调,而间质标志分子N-Cadherin和Vimentin蛋白则表达上调,EMT相关转录激活因子Slug表达量增加;MDA-MB-231细胞中,抑制内源PAK4表达能显著降低细胞的迁移侵袭能力,上调E-Cadherin蛋白表达,下调NCadherin、Vimentin和Slug蛋白的表达。结论:PAK4通过上调Slug促进乳腺癌发生上皮间质转化,可作为抑制乳腺癌转移的分子靶点。
[Abstract]:Objective: to investigate the role of p21 protein activated kinase 4 (PAK4) in epithelial stromal transformation of breast cancer cells. Methods: overexpression of PAK4, in breast cancer MCF7 cells and interference of PAK4 expression in breast cancer MDA-MB-231 cells were detected by migration and invasion assay, and PAK4, was detected by fluorescence quantitative analysis and Western blot analysis. The expression of Vimentin mRNA and protein in E-Cadherinine N-Cadherinn was detected by Western blot. The expression of EMT related transcription activator (Snail,Slug) was detected by Western blotting. Results: after overexpression of PAK4 in MCF7 cells, the ability of cell migration and invasion was significantly increased, and the expression of E-Cadherin protein was down-regulated, while the expression of N-Cadherin and Vimentin proteins was up-regulated. The expression of EMT related transcription activator Slug was increased. Inhibition of endogenous PAK4 expression in MDA-MB-231 cells significantly reduced the migration and invasion ability, up-regulated the expression of E-Cadherin protein, and down-regulated the expression of NCadherin,Vimentin and Slug proteins. Conclusion: PAK4 can be used as a molecular target to inhibit breast cancer metastasis by up-regulating Slug to promote epithelial interstitial transformation in breast cancer.
【作者单位】：吉林省人民医院医学诊治实验中心;
【基金】：吉林省科技发展计划项目(20150520047JH) 吉林省科技厅重点实验室建设专项基金(20150622024JC,20160622008JC)
【分类号】：R737.9

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