Promoter methylation, mutation, and genomic deletion are involved in the decreased NDRG2 expression levels in several cancer cell lines
Promoter methylation, mutation, and genomic deletion are involved in the decreased NDRG2 expression levels in several cancer cell lines
复制标题
启动子甲基化、突变和基因组缺失与多种癌细胞系中 NDRG2 表达水平降低有关。
DOI：
10.1016/j.bbrc.2007.04.089
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发表时间：
2007-06-22
影响因子：
3.1
通讯作者：
Yao, Libo
中科院分区：
文献类型：
--
作者：
Liu, Na;Wang, Lifeng;Yao, Libo
人NDRG 2（N-Myc downstream regulated gene 2）基因在人脑胶质瘤等肿瘤组织中低表达，被认为是一个候选抑癌基因。然而，导致NDRG 2基因失活的机制仍然未知。在本研究中，半定量RT-PCR和蛋白质印迹分析被用来证实NDRG 2 mRNA和蛋白质水平在几种癌细胞系中降低。我们在MCF-7细胞中发现了NDRG 2的杂合性缺失，并表明NDRG 2启动子的突变（在-13 bp（C > T））和甲基化发生在几个癌细胞系中。此外，NDRG 2核心启动子的突变（-13bp（C > T））显著降低NDRG 2活性。最后，我们发现NDRG 2表达在几种乳腺癌组织中降低。出乎意料的是，没有观察到NDRG 2基因的变化。在这里，我们首次描述了NDRG 2基因下调的机制。(c)2007年爱思唯尔公司All rights reserved.
Human NDRG2 (N-Myc downstream regulated gene 2) was identified as a candidate tumor suppressor gene due to its low expression in human glioma and other cancer tissues. However, the mechanisms that lead to inactivation of the NDRG2 gene remain unknown. In the present study, semi-quantitative RT-PCR and Western blot analysis were used to confirm that NDRG2 mRNA and protein levels are decreased in several cancer cell lines. We found heterozygous deletion of NDRG2 in MCF-7 cells, and showed that mutation (at -13 bp (C > T)) and methylation of the NDRG2 promoter occurred in several cancer cell lines. Furthermore, mutation (-13 bp (C > T)) of the NDRG2 core promoter significantly reduced NDRG2 activity. Finally, we showed that NDRG2 expression was decreased in several breast cancer tissues. Unexpectedly, changes in the NDRG2 gene were not observed. Here, we describe for the first time, the mechanisms involved in NDRG2 gene down-regulation. (c) 2007 Elsevier Inc. All rights reserved.