RABEX-5 plays an oncogenic role in breast cancer by activating MMP-9 pathway.
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.
Department of Endocrine and breast Surgery, The First Affiliated Hospital of Chongqing Medical University, China.
Xiang
X
Zhang
Jie
J
Min
Yingjian
Y
Wang
Yan
Y
Li
Hongzhong
H
Li
Qiang
Q
Liu
Xinjie
X
Liang
Peng
P
Mu
Hongyuan
H
Li
D000818:Animals; D001943:Breast Neoplasms / Q000201:enzymology / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000201:enzymology / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D020662:Guanine Nucleotide Exchange Factors / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D064593:Heterografts; D006801:Humans; D007150:Immunohistochemistry; D061986:MCF-7 Cells; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D009857:Oncogenes; D034622:RNA Interference
D020662:Guanine Nucleotide Exchange Factors; C108382:RABGEF1 protein, human; D020780:Matrix Metalloproteinase 9