Luzhna Lidia, Filkowski Jody, Kovalchuk Olga
Department of Biological Sciences, University of Lethbridge, Lethbridge, AB, Canada.
Oncoscience. 2016 Mar 10;3(3-4):88-97. doi: 10.18632/oncoscience.298. eCollection 2016.
The successful treatment of cancer, including breast cancer, depends largely on radiation therapy and proper diagnostics. The effect of ionizing radiation on cells and tissues depends on the radiation dose and energy level, but there is insufficient evidence concerning how tumor cells respond to the low and high doses of radiation that are often used in medical diagnostic and treatment modalities. The purpose of this study was to investigate radiation-induced gene expression changes in the MCF-7 breast adenocarcinoma cell line. Using microarray technology tools, we were able to screen the differential gene expressions profiles between various radiation doses applied to MCF-7 cells. Here, we report the substantial alteration in the expression level of genes after high-dose treatment. In contrast, no dramatic gene expression alterations were noticed after the application of low and medium doses of radiation. In response to a high radiation dose, MCF-7 cells exhibited down-regulation of biological pathways such as cell cycle, DNA replication, and DNA repair and activation of the p53 pathway. Similar dose-dependent responses were seen on the epigenetic level, which was tested by a microRNA expression analysis. MicroRNA analysis showed dose-dependent radiation-induced microRNA expression alterations that were associated with cell cycle arrest and cell death. An increased rate of apoptosis was determined by an Annexin V assay. The results of this study showed that high doses of radiation affect gene expression genetically and epigenetically, leading to alterations in cell cycle, DNA replication, and apoptosis.
癌症（包括乳腺癌）的成功治疗在很大程度上取决于放射治疗和正确的诊断。电离辐射对细胞和组织的影响取决于辐射剂量和能量水平，但关于肿瘤细胞如何应对医学诊断和治疗方式中常用的低剂量和高剂量辐射，证据并不充分。本研究的目的是调查MCF-7乳腺腺癌细胞系中辐射诱导的基因表达变化。使用微阵列技术工具，我们能够筛选应用于MCF-7细胞的不同辐射剂量之间的差异基因表达谱。在此，我们报告高剂量治疗后基因表达水平的显著改变。相比之下，在应用低剂量和中等剂量辐射后，未观察到明显的基因表达改变。响应高辐射剂量时，MCF-7细胞表现出细胞周期、DNA复制和DNA修复等生物途径的下调以及p53途径的激活。在表观遗传水平上也观察到了类似的剂量依赖性反应，这通过微小RNA表达分析进行了测试。微小RNA分析显示剂量依赖性的辐射诱导微小RNA表达改变，这些改变与细胞周期停滞和细胞死亡相关。通过膜联蛋白V测定法确定了凋亡率的增加。本研究结果表明，高剂量辐射在基因和表观遗传水平上影响基因表达，导致细胞周期、DNA复制和凋亡的改变。
