Down-regulation of NDRG1 promotes migration of cancer cells during reoxygenation.
Down-regulation of NDRG1 promotes migration of cancer cells during reoxygenation.
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DOI：
10.1371/journal.pone.0024375
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Chuang EY
中科院分区：
文献类型：
--
作者：
Lai LC;Su YY;Chen KC;Tsai MH;Sher YP;Lu TP;Lee CY;Chuang EY
肿瘤微环境的特征之一是氧波动，这是肿瘤细胞过度增殖、代谢异常以及新生血管系统紊乱造成的。肿瘤的再氧合可诱导氧化应激，从而导致 DNA 损伤和基因组不稳定。尽管细胞对缺氧的反应众所周知，但对复氧时的动态反应知之甚少。为了研究肿瘤适应复氧的转录反应，将乳腺癌MCF-7细胞在0.5％氧气下培养24小时，然后在常氧中复氧24小时。在复氧期间的 0、1、4、8、12 和 24 小时收获细胞。使用 Illumina Human-6 v3 BeadChips 检查复氧后 MCF-7 细胞的转录谱。我们鉴定了 127 个差异表达基因，其中 53.1% 在复氧后上调，46.9% 下调。通路分析显示，HIF-1-α 转录因子网络和经过验证的 C-MYC 转录激活靶点在这些差异表达基因中显着富集。在这些基因中，一部分感兴趣的基因通过定量逆转录 PCR 得到了进一步验证。特别是，人 N-MYC 下调基因 1 (NDRG1) 在复氧时受到高度抑制。 NDRG1 与多种应激和细胞生长调节条件相关。为了确定 NDRG1 是否在复氧中发挥作用，NDRG1 蛋白在 MCF-7 细胞中过表达。再氧合后，NDRG1 的过度表达显着抑制细胞迁移。我们的结果揭示了 MCF-7 细胞在复氧后基因表达的动态性质，并证明 NDRG1 参与肿瘤对复氧的适应。
One characteristic of tumor microenvironment is oxygen fluctuation, which results from hyper-proliferation and abnormal metabolism of tumor cells as well as disorganized neo-vasculature. Reoxygenation of tumors can induce oxidative stress, which leads to DNA damage and genomic instability. Although the cellular responses to hypoxia are well known, little is known about the dynamic response upon reoxygenation. In order to investigate the transcriptional responses of tumor adaptation to reoxygenation, breast cancer MCF-7 cells were cultured under 0.5% oxygen for 24 h followed by 24 h of reoxygenation in normoxia. Cells were harvested at 0, 1, 4, 8, 12, and 24 h during reoxygenation. The transcriptional profile of MCF-7 cells upon reoxygenation was examined using Illumina Human-6 v3 BeadChips. We identified 127 differentially expressed genes, of which 53.1% were up-regulated and 46.9% were down-regulated upon reoxygenation. Pathway analysis revealed that the HIF-1-alpha transcription factor network and validated targets of C-MYC transcriptional activation were significantly enriched in these differentially expressed genes. Among these genes, a subset of interest genes was further validated by quantitative reverse-transcription PCR. In particular, human N-MYC down-regulated gene 1 (NDRG1) was highly suppressed upon reoxygenation. NDRG1 is associated with a variety of stress and cell growth-regulatory conditions. To determine whether NDRG1 plays a role in reoxygenation, NDRG1 protein was overexpressed in MCF-7 cells. Upon reoxygenation, overexpression of NDRG1 significantly inhibited cell migration. Our results revealed the dynamic nature of gene expression in MCF-7 cells upon reoxygenation and demonstrated that NDRG1 is involved in tumor adaptation to reoxygenation.
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影响因子：
2.7
作者：
Guimbellot JS;Erickson SW;Mehta T;Wen H;Page GP;Sorscher EJ;Hong JS
通讯作者：
Hong JS
影响因子：
5.8
作者：
Cartharius, K;Frech, K;Werner, T
通讯作者：
Werner, T
影响因子：
11.2
作者：
Maruyama, Yuichiro;Ono, Mayumi;Kuwano, Michihiko
通讯作者：
Kuwano, Michihiko
影响因子：
2.9
作者：
Cangul H
通讯作者：
Cangul H
影响因子：
3.6
作者：
Corn, Paul G.;El-Deiry, Wafik S.
通讯作者：
El-Deiry, Wafik S.