Published in:
Open Access
01-12-2013 | Research
S100A7 enhances invasion of human breast cancer MDA-MB-468 cells through activation of nuclear factor-κB signaling
Authors:
Huamin Liu, Lei Wang, Xingang Wang, Zhiwei Cao, Qifeng Yang, Kejun Zhang
Published in:
World Journal of Surgical Oncology
|
Issue 1/2013
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Abstract
Background
S100A7 signaling plays a critical role in the pathogenesis and progression of human breast cancers but the precise role and mechanism of S100A7 for tumor invasion remains unclear. in the present study, we investigated whether S100A7 overexpression could be mechanistically associated with the up-regulation of NF-κB, VEGF and MMP-9, resulting in the promotion of breast cancer cell invasion and growth, and vice versa.
Methods
pcDNA3.1-S100A7 cDNA plasmid was constructed and transfected into the MDA-MB-468 cells. 4,5-dimethythiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay was used to detect cell proliferation, Matrigel was used to detect cell mobility and invasion in vitro.The MMP-9 and VEGF expression and levels was detected by western blot and ELISA assay. NF-κB DNA binding activity was detected by Electrophoretic mobility shift assay.
Results
Up-regulation of S100A7 by stable S100A7 cDNA transfection increased cell invasion and proliferation, whereas downregulation of S100A7 by small interfering RNA in S100A7 cDNA-transfected MDA-MB-468 cells decreased cell invasion and proliferation. Consistent with these results, we found that the up-regulation of S100A7 increased NF-κB DNA-binding activity and MMP-9 and VEGF expression. Down-regulation of S100A7 in S100A7 cDNA -transfected decreased NF-κB DNA-binding activity and MMP-9 and VEGF expression.
Conclusions
Our data demonstrate that the S100A7 gene controls the proliferation and invasive potential of human MDA-MB-468 cells through regulation of NF-κB activity and its target genes, such as MMP-9 and VEGF expression. Down-regulation of S100A7 could be an effective approach for the down-regulation and inactivation of NF-κB and its target genes, such as MMP-9 and VEGF expression, resulting in the inhibition of invasion and growth.