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正常和癌变的乳腺和前列腺细胞中与锌稳态相关的基因的表达谱。

Expression profiles of the genes associated with zinc homeostasis in normal and cancerous breast and prostate cells.

机构信息

School of Science, Western Sydney University, Locked Bag 1797, Penrith, NSW 2751, Australia.

Proteomics and Lipidomics Lab, School of Medicine, Western Sydney University, Locked Bag 1797, Penrith, NSW 2751, Australia.

出版信息

Metallomics. 2022 Aug 3;14(8). doi: 10.1093/mtomcs/mfac038.

Abstract

Zn2+ dyshomeostasis is an intriguing phenomenon in breast and prostate cancers, with breast cancer cells exhibiting higher intracellular Zn2+ level compared to their corresponding normal epithelial cells, in contrast to the low Zn2+ level in prostate cancer cells. In order to gain molecular insights into the zinc homeostasis of breast and prostate cancer cells, this study profiled the expression of 28 genes, including 14 zinc importer genes (SLC39A1-14) that encode Zrt/Irt-like proteins 1-14 to transport Zn2+ into the cytoplasm, 10 zinc exporter genes (SLC30A1-10) which encode Zn2+ transporters 1-10 to transport Zn2+ out of the cytoplasm, and 4 metallothionein genes (MT1B, MT1F, MT1X, MT2A) in breast (MCF10A, MCF-7, MDA-MB-231) and prostate (RWPE-1, PC3, DU145) cell lines in response to extracellular zinc exposures at a mild cytotoxic dosage and a benign dosage. The RNA samples were prepared at 0 min (T0), 30 min (T30), and 120 min (T120) in a time course with or without zinc exposure, which were used for profiling the baseline and dynamic gene expression. The up-regulation of MT genes was observed across the breast and prostate cancer cell lines. The expression landscape of SLC39A and SLC30A was revealed by the quantitative reverse transcription polymerase chain reaction data of this study, which sheds light on the divergence of intracellular Zn2+ levels for breast and prostate cancer cells. Taken together, the findings are valuable in unraveling the molecular intricacy of zinc homeostasis in breast and prostate cancer cells.

摘要

锌离子稳态失衡是乳腺癌和前列腺癌中的一个有趣现象,乳腺癌细胞的细胞内锌离子水平高于相应的正常上皮细胞,而前列腺癌细胞中的锌离子水平较低。为了深入了解乳腺癌和前列腺癌细胞的锌离子稳态,本研究对 28 个基因的表达进行了分析,其中包括 14 个锌离子转运体基因(SLC39A1-14),这些基因编码 Zrt/Irt 样蛋白 1-14,将锌离子转运到细胞质中;10 个锌离子外排体基因(SLC30A1-10),这些基因编码 Zn2+转运体 1-10,将锌离子从细胞质中运出;以及 4 个金属硫蛋白基因(MT1B、MT1F、MT1X、MT2A),在乳腺癌(MCF10A、MCF-7、MDA-MB-231)和前列腺癌(RWPE-1、PC3、DU145)细胞系中,对细胞外锌在轻度细胞毒性剂量和良性剂量下的暴露进行了响应。在有无锌暴露的情况下,在时间过程中分别在 0 分钟(T0)、30 分钟(T30)和 120 分钟(T120)制备 RNA 样本,用于分析基础和动态基因表达。在乳腺癌和前列腺癌细胞系中观察到 MT 基因的上调。本研究的定量逆转录聚合酶链反应数据揭示了 SLC39A 和 SLC30A 的表达谱,这为乳腺癌和前列腺癌细胞内锌离子水平的差异提供了线索。综上所述,这些发现对于揭示乳腺癌和前列腺癌细胞中锌离子稳态的分子复杂性具有重要意义。

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