Comparison of the seleno-transcriptome expression between human non-cancerous mammary epithelial cells and two human breast cancer cell lines

Comparison of the seleno-transcriptome expression between human non-cancerous mammary epithelial cells and two human breast cancer cell lines
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DOI:
10.3892/ol.2017.5715
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发表时间:
2017-04-01
期刊:
影响因子:
2.9
通讯作者:
Costantini, Susan
Costantini, Susan
中科院分区:
医学4区
文献类型:
--
作者:
Rusolo, Fabiola;Capone, Francesca;Costantini, Susan

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乳腺癌是导致妇女死亡的第二大常见原因;因此,需要鉴定新的推定标志物,以提高其诊断和预后。硒可以保护乳腺上皮细胞免受DNA氧化损伤,并通过刺激DNA修复和细胞凋亡调节抑制癌变的起始阶段。因此,目前的研究重点是硒蛋白家族及其与乳腺癌的关系。本研究利用逆转录-定量聚合酶链反应对人乳腺癌MCF-7和MDA-MB231细胞系与健康乳腺MCF-10A细胞的硒代转录组表达进行了全面分析。目前的数据显示,与MCF-10A细胞相比,MCF-7和MDA-MB231细胞中存在不同的表达基因:4个下调的基因[谷胱甘肽过氧化物酶(GPX) 1、GPX4、GPX5和GPX7]和3个上调的基因(去碘酶碘甲状腺原氨酸、II型、GPX2和GPX3)。此外,本研究还进行了相互作用研究,以评估下调和上调基因之间的关联,并确定假定的HUB节点,这些节点代表了能够直接控制基因网络的基因之间的关联中心。网络分析显示,除了硒蛋白T外,所有差异调节基因都涉及相同的网络,该网络呈现三个与硒蛋白mrna相互连接的HUB节点,包括TP53,雌激素受体1和catenin- β 1 (CTNNB1)。总的来说,这些数据首次证明了人类乳腺细胞特异性硒mrna的谱,表明这些基因在乳腺癌细胞er阳性或阴性的基础上改变了它们的表达。
Breast cancer is the second most common cause of mortality in women; therefore, the identification of novel putative markers is required to improve its diagnosis and prognosis. Selenium is known to protect mammary epithelial cells from oxidative DNA damage, and to inhibit the initiation phase of carcinogenesis by stimulating DNA repair and apoptosis regulation. Consequently, the present study has focused attention on the selenoprotein family and their involvement in breast cancer. The present study performed a global analysis of the seleno-transcriptome expression in human breast cancer MCF-7 and MDA-MB231 cell lines compared with healthy breast MCF-10A cells using reverse transcription-quantitative polymerase chain reaction. The present data revealed the presence of differently expressed genes in MCF-7 and MDA-MB231 cells compared with MCF-10A cells: Four downregulated [glutathione peroxidase (GPX) 1, GPX4, GPX5 and GPX7] and three upregulated (deiodinase iodothyronine, type II, GPX2 and GPX3) genes. Additionally, interactomic investigation were performed by the present study to evaluate the association between the downregulated and upregulated genes, and to identify putative HUB nodes, which represent the centers of association between the genes that are capable of direct control over the gene networks. Network analysis revealed that all differentially regulated genes, with the exception of selenoprotein T, are implicated in the same network that presents three HUB nodes interconnected to the selenoprotein mRNAs, including TP53, estrogen receptor 1 and catenin-beta 1 (CTNNB1). Overall, these data demonstrated for the first time, a profile of seleno-mRNAs specific for human breast cells, indicating that these genes alter their expression on the basis of the ER-positivity or negativity of breast cancer cells.