Overexpression of N-Myc downstream-regulated gene 2 (NDRG2) regulates the proliferation and invasion of bladder cancer cells in vitro and in vivo.

Overexpression of N-Myc downstream-regulated gene 2 (NDRG2) regulates the proliferation and invasion of bladder cancer cells in vitro and in vivo.
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DOI:
10.1371/journal.pone.0076689
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发表时间:
2013
期刊:
影响因子:
3.7
通讯作者:
Wu G
Wu G
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Li R;Yu C;Jiang F;Gao L;Li J;Wang Y;Beckwith N;Yao L;Zhang J;Wu G

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N-Myc下游调节基因2(NDRG 2)是一个候选的肿瘤抑制基因,在控制肿瘤生长中起重要作用。本研究旨在探讨NDRG 2基因在膀胱癌组织和几种膀胱癌细胞系中的表达及其临床病理意义。采用免疫组化方法对97例膀胱癌和15例正常膀胱组织进行回顾性分析。用LEN-NDRG 2或LEN-LacZ感染人膀胱癌细胞系T24。通过细胞生长曲线、肿瘤生长曲线、流式细胞术、western blot和Transwell法检测NDRG 2过表达对T24细胞和T24裸鼠移植瘤的影响。NDRG 2在正常膀胱组织中呈高表达,而在癌组织中无表达或极少表达(χ2=8.761,p < 0.01)。NDRG 2表达与肿瘤分级、病理分期呈负相关(r=-0.248,p < 0.05),与c-myc表达呈负相关(r=-0.454,p< 0.001)。NDRG 2在3种BC细胞系中均呈低表达。LEN-NDRG 2感染T24细胞后,在体内外均表现出增殖抑制作用,NDRG 2过表达可抑制肿瘤的生长和体外侵袭。
N-Myc downstream-regulated gene 2 (NDRG2) is a candidate tumor suppressor gene, which plays an important role in controlling tumor growth. The aim of this study was to investigate the expression of NDRG2 gene in bladder cancer (BC) tissues and several bladder cancer cell lines, and to seek its clinical and pathological significance. Ninety-seven bladder carcinoma and 15 normal bladder tissue sections were analyzed retrospectively with immunohistochemistry. The human bladder cancer cell line T24 was infected with LEN-NDRG2 or LEN-LacZ. The effects of NDRG2 overexpression on T24 cells and T24 nude mouse xenografts were measured via cell growth curves, tumor growth curves, flow cytometric analysis, western blot and Transwell assay. NDRG2 was highly expressed in normal bladder tissue, but absent or rarely expressed in cacinomatous tissues (χ2=8.761, p < 0.01). The NDRG2 level was negatively correlated with tumor grade and pathologic stage(r=-0.248, p < 0.05), as well as increased c-myc level (r=-0.454, p< 0.001). The expression of NDRG2 was low in the three BC cell lines. T24 cells infected with LEN-NDRG2 showed inhibition of proliferation both in vitro and in vivo, and NDRG2 overexpression can inhibit tumor growth and invasion in vitro.
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