RABEX-5 plays an oncogenic role in breast cancer by activating MMP-9 pathway

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• 作者：Xiang Zhang (17) (18)
  Jie Min (18)
  Yingjian Wang (18)
  Yan Li (18)
  Hongzhong Li (17) (18)
  Qiang Liu (18)
  Xinjie Liang (17) (18)
  Peng Mu (18)
  Hongyuan Li (18)
  
• 关键词：RABEX ; 5 ; Breast cancer ; Oncogene ; RNAi
• 刊名：Journal of Experimental & Clinical Cancer Research
• 出版年：2013
• 出版时间：December 2013
• 年：2013
• 卷：32
• 期：1
• 全文大小：1268KB
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• 作者单位：Xiang Zhang (17) (18)
  Jie Min (18)
  Yingjian Wang (18)
  Yan Li (18)
  Hongzhong Li (17) (18)
  Qiang Liu (18)
  Xinjie Liang (17) (18)
  Peng Mu (18)
  Hongyuan Li (18)
  
  17. Molecular Oncology and Epigenetics Laboratory, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China
  18. Department of Endocrine and breast Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China
  
• ISSN：1756-9966

文摘

Background RABEX-5, a guanine nucleotide exchange factor (GEF) for RAB-5, plays an important role in cell mobility and altered expression associated with tumor metastasis. This study aimed to investigate the role of RABEX-5 in proliferation and metastasis of breast cancer in vitro and ex vivo. Methods RABEX-5 expression was examined in breast cancer, benign tumor and normal breast tissues by immunohistochemistry and western blot. Two stable cell lines were established, the MCF-7/NC negative control cell line and the MCF-7/KD cell line, which stably expressed an RNA interference (RNAi) construct that induced downregulation of RABEX-5 expression. These cell lines were utilized to evaluate the role of RABEX-5 in cell proliferation and migration in vitro and tumorigenicity in vivo. The possible role of RABEX-5 in the regulation of matrix metallopeptidase 9 (MMP-9) was evaluated using western blot and real-time PCR. Results RABEX-5 expression was found to be significantly higher in breast cancer tissues compared with benign tumor and normal breast tissues. High levels of RABEX-5 expression were associated with axillary lymph node metastasis. In addition, RABEX-5 silencing significantly reduced cancer cell proliferation, colony formation and migration ability in vitro and inhibited tumor growth in vivo. RABEX ? knockdown also attenuated the migration of breast cancer cells via modulation of MMP-9 transcriptional activity. Conclusions Our results indicate that RABEX-5 plays an oncogenic role in breast cancer by modulating the proliferation and metastasis potential of breast cancer cells. Thus, RABEX-5 is a promising prognostic indicator for patients with breast cancer.