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

Journal of Experimental & Clinical Cancer Research

Hongyuan Li¹  Peng Mu¹  Xinjie Liang¹  Qiang Liu¹  Hongzhong Li¹  Yan Li¹  Yingjian Wang¹  Jie Min¹  Xiang Zhang¹ 

[1] Department of Endocrine and breast Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China

关键词: RNAi;    Oncogene;    Breast cancer;    RABEX-5;   

Others  :  824793
DOI  :  10.1186/1756-9966-32-52

 received in 2013-04-22, accepted in 2013-08-07,  发布年份 2013

【 摘 要 】

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 −5 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.

【 授权许可】

   
2013 Zhang et al.; licensee BioMed Central Ltd.

【 图 表 】

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