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中国癌症防治杂志

中国癌症防治杂志 ›› 2018, Vol. 10 ›› Issue (2): 136-140.doi: 10.3969/j.issn.1674-5671.2018.02.14

• 临床研究 • 上一篇    下一篇

RSK4与Ki-67、cyclin D1、CXCR4、E-cadherin在乳腺癌裸鼠移植瘤中的相关性研究

  

  1. 广西医科大学附属肿瘤医院乳腺外科一病区；广西医科大学研究生院
  • 出版日期:2018-04-25 发布日期:2018-06-13
  • 通讯作者: 刘剑仑 E-mail：jianlunliu@hotmail.com
  • 基金资助:

    国家自然科学基金资助项目（30960427）

Correlations of RSK4 expression with Ki-67，cyclin D1，CXCR4 and E-cadherin levels in an in vivo tumor model of breast cancer

  • Online:2018-04-25 Published:2018-06-13

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被引次数

2

摘要：

目的 分析乳腺癌裸鼠移植瘤中核糖体 S6蛋白激酶 4（ribosomal protein S6 kinase 4，RSK4） 与Ki-67、cyclin D1、CXCR4、E-cadherin表达的相关性，进一步探讨RSK4在乳腺癌发展中的作用机制。方法 将转染siRNA （RSK4-RNAi-LV）的MCF-7细胞（实验组）、转染siRNA （NC-GFP-LV）的MCF-7细胞（阴性对照组）和未转染的MCF-7细胞（空白对照组）分别接种至裸鼠乳腺脂肪垫下，建立乳腺癌裸鼠移植瘤模型，剥离裸鼠移植瘤；采用免疫组织化学法检测移植瘤标本中增殖因子RSK4、Ki-67、cyclin D1 及侵袭因子CXCR4、E-cadherin蛋白的表达。结果 实验组RSK4、E-cadherin蛋白的表达水平分别为（3.2±0.5）％、（28.2±0.7）％，明显低于空白对照组的（36.7±3.4）％、（51.7±4.2）％和阴性对照组的（61.1±5.1）％、（49.2±3.8）％，差异有统计学意义（F=56.79，61.89，P＜0.05）。实验组Ki-67、cyclin D1、CXCR4蛋白的表达水平分别为（67.8±5.8）％、（61.7±4.6）％、（56.3±3.9）％，明显高于空白对照组的（34.5±1.4）％、（29.7±2.5）％、（30.7±3.1）％和阴性对照组的（29.8±1.9）％、（35.7±4.6）％、（28.5±3.7）％，差异有统计学意义（F=45.24，52.16，61.24，P＜0.05）。相关性分析显示，RSK4与 Ki-67、cyclin D1、CXCR4表达呈负相关（r=-0.857，-0.826，-0.867，P<0.001），与E-cadherin表达呈正相关（r=0.879，P<0.001）。 结论 RSK4可能通过调节CXCR4、Ki-67、CyclinD1和E-cadherin肿瘤相关因子的表达，在乳腺癌在乳腺癌生长及转移过程中发挥作用。

关键词: 乳腺肿瘤, RSK4, Ki-67, cyclin D1, CXCR4, E-cadherin, MCF-7细胞株, 移植瘤

Abstract:

Objective To investigate the relationship between RSK4 expression and Ki-67，cyclin D1，CXCR4 and E-cadherin levels in an in vivo tumor model of breast cancer in order to explore the mechanism of breast cancer development. Methods The experimental group of nude mice was subcutaneously injected with MCF-7 cells transfected with siRNA （RSK4-RNAi-LV），while the negative control group was subcutaneously injected with MCF-7 cells transfected with siRNA （NC-GFP-LV），and a blank control group was subcutaneously injected with MCF-7 cells alone. Expression of RSK4，Ki-67，cyclin D1，CXCR4 and E-cadherin in samples of transplanted tumors was observed by immunohistochemistry. Results Levels of RSK4 and E-cadherin protein were 3.2±0.5% and 28.2±0.7% in the experimental group，which was significantly lower than in the blank control group （36.7±3.4%，51.7±4.2%） and negative control group（61.1±5.1%，49.2±3.8%） （F=56.79 and 61.89，P<0.05）. Similar，expression levels of Ki-67，cyclin D1，and CXCR4 in the experimental group were，respectively，67.8±5.8%，61.7±4.6%，and 56.3±3.9%，which were significantly higher than in the blank control group（34.5±1.4%，29.7±2.5%，30.7±3.1%） and the negative control group （29.8±1.9%，35.7±4.6%，28.5±3.7%） （F=45.24，52.16，and 61.24，P<0.05）. RSK4 protein expression showed a significant negative correlation with Ki-67（r=-0.857，P<0.001），cyclin D1（r=-0.826，P<0.001） and CXCR4 （r=-0.867，P<0.001）. RSK4 protein expression showed a significant positive correlation with E-cadherin（r=0.879，P<0.001）. Conclusions RSK4 knockdown may affect the expression of tumor proliferation factor and invasion factor，promoting the proliferation and metastasis of breast cancer cells. RSK4 may regulate genes in a way that promotes breast cancer cell proliferation and invasion，including up-regu-lation of CXCR4，Ki-67，and CyclinD1，as well as down-regulation of E-cadherin.

Key words: Breast neoplasms, RSK4, Ki-67, cyclin D1, CXCR4, E-cadherin, MCF-7 cell line, Transplantation tumor