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首页> 外文期刊>Cell cycle >Oct-1 modifies S100A4 exchange between intra- and extracellular compartments in Namalwa cells and increases their sensitivity to glucocorticoids
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Oct-1 modifies S100A4 exchange between intra- and extracellular compartments in Namalwa cells and increases their sensitivity to glucocorticoids

机译:Oct-1修饰Namalwa细胞内和细胞外区室之间的S100A4交换,并增加其对糖皮质激素的敏感性

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摘要

S100A4, a small intra- and extracellular Ca2+-binding protein, is involved in tumor progression and metastasis with S100A4 level shown to be correlated with tumor cells metastatic potential. Simultaneously, Octamer transcription factor 1 (Oct-1) regulates a wide range of genes and participates in tumor cell progression with high Oct-1 level associated with a poor prognosis for different tumors. In this study, following the establishment of Oct-1 binding site, we used Burkit lymphoma B cells (Namalwa cells) which express different isoforms of Oct-1 (Oct-1A, Oct-1L and Oct-1X) to investigate the role of Oct-1 in S100A4 expression and sustaining intra- and extra-cellular S100A4 levels. As antitumor agents, we used dexamethasone which effect is mediated by the activation of intracellular glucocorticoid receptors and camptothecin which molecular target is nuclear DNA topoisomerase I (TOP1). We established that, firstly, the most significant increase in S100A4 gene expression has been demonstrated in the cells transfected with Oct-1A. Secondly, we have established that high level of Oct-1 and decreased intracellular S100A4 level decline the survival of Namalwa cells under dexamethasone treatment. Thirdly, we have shown that the tumor cells transformation by different Oct-1 isoforms retained those cells' sensitivity to the antitumor effect of combined dexamethasone and camptothecin. In contrast, in the non-transformed Namalwa cells, dexamethasone decreased the camptothecin effect on the cells survivorship, thus, emphasizing Oct-1 role in the regulation of cell response to different antitumor agents. The results identify a necessity to consider Oct-1 level for combined chemotherapeutic drug treatment.
机译:S100A4是一种小的细胞内和细胞外Ca2 +结合蛋白,参与肿瘤的进展和转移,S100A4的水平与肿瘤细胞的转移潜能相关。同时,Octamer转录因子1(Oct-1)调节广泛的基因,并以高Oct-1水平参与肿瘤细胞的进展,与不同肿瘤的预后不良相关。在这项研究中,建立了Oct-1结合位点后,我们使用了Burkit淋巴瘤B细胞(Namalwa细胞)来表达Oct-1的不同同工型(Oct-1A,Oct-1L和Oct-1X),以研究其作用。 Oct-1在S100A4中的表达并维持细胞内和细胞外S100A4的水平。作为抗肿瘤药,我们使用了地塞米松,地塞米松的作用是通过激活细胞内糖皮质激素受体和喜树碱来实现的,而喜树碱的分子靶标是核DNA拓扑异构酶I(TOP1)。我们确定,首先,已在用Oct-1A转染的细胞中证明了S100A4基因表达的最显着增加。其次,我们已经确定,在地塞米松处理下,高水平的Oct-1和降低的细胞内S100A4水平会降低Namalwa细胞的存活率。第三,我们已经表明,通过不同的Oct-1亚型转化的肿瘤细胞保留了这些细胞对地塞米松和喜树碱联合抗肿瘤作用的敏感性。相反,在未转化的Namalwa细胞中,地塞米松降低了喜树碱对细胞存活的影响,因此强调了Oct-1在调节对不同抗肿瘤药的细胞应答中的作用。结果表明有必要考虑Oct-1水平用于联合化疗药物治疗。

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