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人非癌性乳腺上皮细胞与两种人乳腺癌细胞系之间硒转录组表达的比较。

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

作者信息

Rusolo Fabiola, Capone Francesca, Pasquale Raffaella, Angiolillo Antonella, Colonna Giovanni, Castello Giuseppe, Costantini Maria, Costantini Susan

机构信息

Oncology Research Center of Mercogliano, National Cancer Institute 'G. Pascale Foundation', IRCCS, I-80131 Naples, Italy.

Department of Medicine and Health Sciences, University of Molise, I-86100 Campobasso, Italy.

出版信息

Oncol Lett. 2017 Apr;13(4):2411-2417. doi: 10.3892/ol.2017.5715. Epub 2017 Feb 13.

Abstract

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-β1 (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.

摘要

乳腺癌是女性第二大常见死因;因此,需要鉴定新的潜在标志物以改善其诊断和预后。已知硒可保护乳腺上皮细胞免受氧化性DNA损伤,并通过刺激DNA修复和凋亡调控来抑制致癌作用的起始阶段。因此,本研究聚焦于硒蛋白家族及其在乳腺癌中的作用。本研究使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细胞中的硒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细胞中存在差异表达的基因:四个下调基因[谷胱甘肽过氧化物酶(GPX)1、GPX4、GPX5和GPX7]和三个上调基因[脱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组学研究,以评估下调和上调基因之间的关联,并鉴定潜在的枢纽节点,这些节点代表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,除硒蛋白T外,所有差异调节基因都参与了同一个网络,该网络有三个与硒蛋白mRNA相互连接的枢纽节点,包括TP53、雌激素受体1和连环蛋白-β1(CTNNB1)。总体而言,这些数据首次证明了人乳腺细胞特异性的硒mRNA谱,表明这些基因根据乳腺癌细胞的雌激素受体阳性或阴性改变其表达。

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