NDRG2 抑制肾透明细胞癌细胞 A-498 的增殖。
NDRG2 suppresses the proliferation of clear cell renal cell carcinoma cell A-498.
机构信息
Department of Urology, Tangdu Hospital, the Fourth Military Medical University, Xi'an, China.
出版信息
J Exp Clin Cancer Res. 2010 Jul 30;29(1):103. doi: 10.1186/1756-9966-29-103.
BACKGROUND
Recently, the anti-tumor activity of N-myc downstream-regulated gene 2 (NDRG2) was shown decreased expression in clear cell renal cell carcinoma (CCRCC), but the role of the down-expression of NDRG2 has not been described.
METHODS
The NDRG2 recombinant adenovirus plasmid was constructed. The proliferation rate and NDRG2 expression of cell infected with recombinant plasmid were mesured by MTT, Flow cytometry analysis and western blot.
RESULTS
The CCRCC cell A-498 re-expressed NDRG2 when infected by NDRG2 recombinant adenovirus and significantly decreased the proliferation rate. Fluorescence activated cell sorter analysis showed that 25.00% of cells expressed NDRG2 were in S-phase compared to 40.67% of control cells, whereas 62.08% of cells expressed NDRG2 were in G1-phase compared to 54.39% of control cells (P < 0.05). In addition, there were much more apoptotic cells in NDRG2-expressing cells than in the controls (P < 0.05). Moreover, upregulation of NDRG2 protein was associated with a reduction in cyclin D1, cyclin E, whereas cyclinD2, cyclinD3 and cdk2 were not affected examined by western blot. Furthermore, we found that p53 could upregulate NDRG2 expression in A-498 cell.
CONCLUSIONS
We found that NDRG2 can inhibit the proliferation of the renal carcinoma cells and induce arrest at G1 phase. p53 can up-regulate the expression of NDRG2. Our results showed that NDRG2 may function as a tumor suppressor in CCRCC.
背景
最近，研究表明 N- MYC 下游调节基因 2（NDRG2）在肾透明细胞癌（CCRCC）中的表达降低，但尚未描述 NDRG2 表达降低的作用。
方法
构建 NDRG2 重组腺病毒质粒。通过 MTT、流式细胞术分析和 Western blot 检测感染重组质粒的细胞增殖率和 NDRG2 表达。
结果
CCRCC 细胞 A-498 感染 NDRG2 重组腺病毒后重新表达 NDRG2，增殖率明显降低。荧光激活细胞分选分析显示，表达 NDRG2 的细胞中有 25.00％处于 S 期，而对照细胞中有 40.67％，表达 NDRG2 的细胞中有 62.08％处于 G1 期，而对照细胞中有 54.39％（P <0.05）。此外，表达 NDRG2 的细胞中凋亡细胞比对照组多（P <0.05）。此外，Western blot 检测发现，NDRG2 蛋白的上调与细胞周期蛋白 D1、E 的减少有关，而细胞周期蛋白 D2、D3 和 cdk2 不受影响。此外，我们发现 p53 可以上调 A-498 细胞中 NDRG2 的表达。
结论
我们发现 NDRG2 可抑制肾癌细胞的增殖并诱导其停滞在 G1 期。p53 可以上调 NDRG2 的表达。我们的结果表明，NDRG2 可能在 CCRCC 中作为肿瘤抑制因子发挥作用。
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