<em>NDRG</em>2 inhibits the proliferation of breast cancer cells via regulating β-catenin expression and nuclear translocation

周晓雷; 朱重悦; 张世光

doi:10.19401/j.cnki.1007-3639.2016.12.004

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NDRG2 inhibits the proliferation of breast cancer cells via regulating β-catenin expression and nuclear translocation

更新时间：2025-12-31

- NDRG2 inhibits the proliferation of breast cancer cells via regulating β-catenin expression and nuclear translocation
- China Oncology Vol. 26, Issue 12, Pages: 981-988(2016)
- 作者机构：
  
  河北科技大学生物实验中心,河北,石家庄,050018
- 作者简介：
- 基金信息：
- DOI：10.19401/j.cnki.1007-3639.2016.12.004
  CLC：
- Published Online：23 January 2017，
  
  Published：23 January 2016
- 稿件说明：
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周晓雷,朱重悦,张世光,等.

周晓雷, 朱重悦, 张世光. NDRG2 inhibits the proliferation of breast cancer cells via regulating β-catenin expression and nuclear translocation[J]. China Oncology, 2016, 26(12): 981-988.
周晓雷,朱重悦,张世光,等. DOI： 10.19401/j.cnki.1007-3639.2016.12.004.

周晓雷, 朱重悦, 张世光. NDRG2 inhibits the proliferation of breast cancer cells via regulating β-catenin expression and nuclear translocation[J]. China Oncology, 2016, 26(12): 981-988. DOI： 10.19401/j.cnki.1007-3639.2016.12.004.

摘要

背景与目的：乳腺癌是女性发病率最高的恶性肿瘤之一，肿瘤细胞的恶性增殖是造成患者死亡的重要原因。本研究利用具有相同遗传背景但不同增殖能力的乳腺癌细胞模型，研究N-myc下游调节基因2(N-myc downstream regulated gene 2，NDRG2)调控乳腺癌细胞增殖的作用及分子机制。方法：通过蛋白［质］印迹法(Western blot)检测MCF-7/LM-MCF-7细胞中NDRG2蛋白表达水平；构建NDRG2真核表达载体及siRNA干扰片段，通过转染上调或沉默NDRG2表达，流式细胞实验检测细胞增殖能力，Western blot检测β-连环蛋白(β-catenin)表达，免疫荧光染色检测β-catenin细胞定位；共转染MCF-7细胞NDRG2 siRNA和pCMV-Tcfδ，流式细胞实验检测细胞增殖能力。结果：NDRG2的蛋白表达水平同乳腺癌细胞增殖能力负相关；在增殖的LMMCF-7细胞中上调NDRG2表达，细胞增殖指数(proliferation index，PI)由47.18%下降至31.78%(P0.001)；在低增殖的MCF-7细胞中沉默NDRG2表达，PI由32.00%上升至52.59%(P0.001)；Western blot及免疫荧光结果显示，NDRG2可抑制β-catenin表达，并抑制其聚集入核；流式细胞检测结果显示，共转染siRNA和pCMV-Tcfδ的MCF-7细胞增殖能力未增强，进一步说明NDRG2是通过抑制β-catenin的转录调节作用抑制肿瘤细胞增殖。结论：在乳腺癌细胞中，NDRG2的表达水平下调，导致β-catenin聚集入核，并激活下游靶基因，促进乳腺癌细胞增殖。此分子机制对阐明乳腺癌细胞增殖调控机制具有重要意义。

Abstract

Background and purpose: Breast cancer is one of the most common malignant diseases in women and its malignant proliferation is the major cause of death. To investigate the effects of N-myc downstream regulated gene 2 (NDRG2) on proliferation of breast cancer cells by using two parallel cell lines (MCF-7 and LM-MCF-7) with different metastatic abilities. Methods: The expression level of NDRG2 in breast cancer cells was detected by Western blot. The effects of overexpressing (or down-regulating) NDRG2 on proliferation of breast cancer cells were investigated by flow cytometry. The expression and location of β-catenin were detected by Western blot and immunofluorescence respectively. NDRG2 blocking the transcription activity of β-catenin was investigated via co-transfecting MCF-7 cells with NDRG2 siRNA and pCMV-Tcfδ (lacking the portion responsible for the protein binding to DNA). Results: The expression level of NDRG2 was negatively related to the proliferation ability of breast cancer cells. Over-expressing NDRG2 (or down-regulating) via transfecting LM-MCF-7 (or MCF-7) cells with pCMV-NDRG2 (or NDRG2 siRNA) could inhibit (or promote) cell proliferation. Interestingly

the results of Western blot

immunofluorescence and flow cytometry revealed that down-regulation of NDRG2 resulted from the down-regulation of β-catenin and blocking its nuclear translocation

which led to losing control of the proliferation of breast cancer cells. Conclusion: NDRG2 inhibit the proliferation of breast cancer cells via down-regulating the expression of β-catenin and blocking its nuclear translocation

which is significant for exploring the molecular mechanism of proliferation of breast cancer cells.

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NDRG2 inhibits the proliferation of breast cancer cells via regulating β-catenin expression and nuclear translocation

DOI：10.19401/j.cnki.1007-3639.2016.12.004

摘要

Abstract

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Keywords

references