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首页> 外文期刊>Molecular and Cellular Biology >The Cochaperone p23 Differentially Regulates Estrogen Receptor Target Genes and Promotes Tumor Cell Adhesion and Invasion
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The Cochaperone p23 Differentially Regulates Estrogen Receptor Target Genes and Promotes Tumor Cell Adhesion and Invasion

机译：伴侣蛋白p23差异调节雌激素受体靶基因，并促进肿瘤细胞的粘附和侵袭。

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The cochaperone p23 plays an important role in estrogen receptor alpha (ER) signal transduction. In this study, we investigated how p23 regulates ER target gene activation and affects tumor growth and progression. Remarkably, we found that changes in the expression of p23 differentially affected the activation of ER target genes in a manner dependent upon the type of DNA regulatory element. p23 overexpression enhanced the expression of the ER target genes cathepsin D and pS2, which are regulated by direct DNA binding of ER to estrogen response elements (ERE). In contrast, the expression of other target genes, including c-Myc, cyclin D1, and E2F1, to which ER is recruited indirectly through its interaction with other transcription factors remains unaffected by changes in p23 levels. The p23-induced expression of pS2 is associated with enhanced recruitment of ER to the ERE in the promoter, whereas ER recruitment to the ERE-less c-Myc promoter does not respond to p23. Intriguingly, p23-overexpressing MCF-7 cells exhibit increased adhesion and invasion in the presence of fibronectin. Our findings demonstrate that p23 differentially regulates ER target genes and is involved in the control of distinct cellular processes in breast tumor development, thus revealing novel functions of this cochaperone.
机译：伴侣蛋白p23在雌激素受体α（ER）信号转导中起重要作用。在这项研究中，我们研究了p23如何调节ER靶基因激活并影响肿瘤的生长和发展。值得注意的是，我们发现p23表达的变化以取决于DNA调控元件类型的方式差异性地影响ER靶基因的激活。 p23过表达增强了ER靶基因组织蛋白酶D和pS2的表达，这由ER与雌激素反应元件（ERE）的直接DNA结合调控。相反，其他靶基因的表达，包括c-Myc，细胞周期蛋白D1和E2F1，通过与其他转录因子的相互作用而间接招募到ER的基因不受p23水平变化的影响。 p23诱导的pS2表达与启动子中ER向ERE的增强募集有关，而ER向缺少ERE的c-Myc启动子的募集不响应p23。有趣的是，在纤连蛋白存在下，过度表达p23的MCF-7细胞显示出增加的粘附和侵袭。我们的发现表明，p23差异性调控ER靶基因，并参与乳腺肿瘤发展过程中不同细胞过程的控制，从而揭示了该伴侣蛋白的新功能。

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