A significant gap in the knowledge of zinc homeostasis exists for breast cancer cells. In this study, we investigated the transcriptomic response of the luminal breast cancer cells (MCF-7) to the exposure of extracellular zinc using next-generation RNA sequencing. The dataset was collected for three time points (T0, T30, and T120) in the time course of zinc treatment, which revealed the dramatic increase, up to 869-fold, of the gene expression for metallothioneins (MT1B, MT1F, MT1X, and MT2A) and the zinc exporter ZnT1 (SLC30A1) at T30, continuingly through to T120. The similar dynamic expression pattern was found for the autophagy-related gene (VMP1) and numerous genes for zinc finger proteins (e.g. RNF165, ZNF365, ZBTB2, SNAI1, ZNF442, ZNF547, ZNF563, and ZNF296). These findings point to the all-hands-on-deck strategy adopted by the cancer cells for maintaining zinc homeostasis. The stress responsive genes encoding heat shock proteins (HSPA1A, HSPA1B, HSPA1L, HSPA4L, HSPA6, HSPA8, HSPH1, HSP90AA1, and HSP90AB1) and the MTF-1 biomarker genes (AKR1C2, CLU, ATF3, GDF15, HMOX1, MAP1A, MAFG, SESN2, and UBC) were also differentially up-regulated at T120, suggesting a role of heat shock proteins and the MTF-1 related stress proteins in dealing with zinc exposure. It is for the first time that the gene encoding Polo-like kinase 2 (PLK2) was found to be involved in zinc-related response. The top differentially expressed genes were validated by qRT-PCR and further extended to the basal type breast cancer cells (MDA-MB-231). It was found that the expression level of SLC30A1 in MDA-MB-231 was higher than MCF-7 in response to zinc exposure. Taken together, the findings contribute to our knowledge and understanding of zinc homeostasis in breast cancer cells.

中文翻译：

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通过下一代 RNA 测序对 MCF-7 乳腺癌细胞锌稳态的转录组学见解。

对于乳腺癌细胞，锌稳态知识存在显着差距。在这项研究中，我们使用下一代 RNA 测序研究了管腔乳腺癌细胞 (MCF-7) 对细胞外锌暴露的转录组反应。在锌处理的时间过程中收集了三个时间点（T0、T30 和 T120）的数据集，这表明金属硫蛋白（MT1B、MT1F、MT1X 和MT2A) 和锌出口国 ZnT1 (SLC30A1) 在 T30，继续到 T120。在自噬相关基因 (VMP1) 和许多锌指蛋白基因（例如 RNF165、ZNF365、ZBTB2、SNAI1、ZNF442、ZNF547、ZNF563 和 ZNF296）中发现了类似的动态表达模式。这些发现表明癌细胞为维持锌稳态而采取的全员参与策略。编码热休克蛋白的应激反应基因（HSPA1A、HSPA1B、HSPA1L、HSPA4L、HSPA6、HSPA8、HSPH1、HSP90AA1 和 HSP90AB1）和 MTF-1 生物标志物基因（AKR1C2、CLU、ATF3、GDF15、HMOX1、MAP1A、MAFG SESN2 和 UBC）在 T120 也有差异上调，表明热休克蛋白和 MTF-1 相关应激蛋白在处理锌暴露中的作用。这是首次发现编码 Polo 样激酶 2 (PLK2) 的基因参与锌相关反应。通过 qRT-PCR 验证了最高差异表达的基因，并进一步扩展到基底型乳腺癌细胞 (MDA-MB-231)。发现 SLC30A1 在 MDA-MB-231 中的表达水平高于 MCF-7，以响应锌暴露。总之，这些发现有助于我们了解和理解乳腺癌细胞中的锌稳态。