These in vivo data were consistent with the in vitro results and confirmed that the silencing of RABEX-5 inhibits breast cancer growth and progression by modulating MMP-9 transcriptional activity. In summary, RABEX-5

plays an oncogenic role in breast cancer. Figure 4 Gene silencing of RABEX-5 inhibits breast cancer growth in vivo. (A), MCF-7/KD cells and MCF-7/NC cells were injected subcutaneously into nude mice. Mice were sacrificed after 4 weeks from transplant. (B-D), Tumor Selleckchem Metformin volume and tumor weight were measured after dissection. (B), Tumor volume were recorded 0, 7, 14, 21 and 28 days after after tumor cell inoculated, and the final tumor weight (D) and volume (C) were determined. (E), MMP-9 protein levels in transplantation tumor samples were analyzed by western blot. GAPDH was used as an internal control. selleck products (F),The immunohistochemistry analysis

of MMP-9 expression in tumors derived from MCF-7/NC group and MCF-7/KD group. Original magnification, ×40. The asterisk indicates statistical significant difference (P<0.05). Discussion RABEX-5 is a guanine nucleotide exchange factor (GEF) for RAB-5 [13], a small GTPase that regulates early endosome fusion and endocytosis [17–21]. RABEX-5 was identified as an interactor of Rabaptin-5 and was found to possess GEF activity toward RAB-5 and related GTPases; both Rabaptin-5 and RABEX-5 are essential for RAB-5-driven endosome fusion. Previous studies have reported that RABEX-5 can specifically bind to the active form of RAB-5, thereby regulating the docking and fusion of endosomal membranes, the motility of endosomes and intracellular signal transduction [22]. It has been demonstrated that the expression of RAB-5 proteins was associated with the development

of various malignant tumors of the breast, ovary, and lung [23–25]. However, previous studies have not yet investigated the association between RABEX-5 expression and cancer. In the present study, we demonstrated that RABEX-5 was overexpressed in breast cancer tissues and breast cancer cells; in addition, the influence of RABEX-5 on the biological behavior of breast cancer see more cells in vitro and in vivo was investigated. Our results argue that RABEX-5 may have an oncogenic effect on breast cancer. In this study, we found that RABEX-5 was clearly overexpressed in all 5 breast cancer cell lines (MCF-7, MDA-MB-231, T47D, BT549, and SKBR3) and breast cancer tissues that were tested. In contRast, RABEX-5 was expressed at low levels in benign breast tumor tissues and normal breast tissues. The high expression of RABEX-5 in breast cancer cells was consistent with the results obtained from other tumors [14], which indicates that RABEX-5 was involved in tumorigenesis.