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Published in: Breast Cancer Research 5/2010

Open Access 01-10-2010 | Research article

Silencing of the IKKε gene by siRNA inhibits invasiveness and growth of breast cancer cells

Authors: Bin Qin, Kun Cheng

Published in: Breast Cancer Research | Issue 5/2010

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Abstract

Introduction

IκB kinase ε (IKKε) is a member of the IKK family that plays an important role in the activation of NF-κB. Overexpressed in more than 30% of breast cancers, IKKε has been recently identified as a potential breast cancer oncogene. The purpose of the present study is to examine the therapeutic potential of IKKε siRNA on human breast cancer cells.

Methods

Eight siRNAs targeting different regions of the IKKε mRNA were designed, and the silencing effect was screened by quantitative real-time RT-PCR. The biological effects of synthetic siRNAs on human breast cancer cells were investigated by examining the cell proliferation, migration, invasion, focus formation, anchorage-independent growth (via soft agar assay), cell cycle arrest, apoptosis (via annexing binding), NF-κB basal level, and NF-κB-related gene expressions upon the IKKε silencing.

Results

Silencing of IKKε in human breast cancer cells resulted in a decrease of focus formation potential and clonogenicity as well as in vitro cell migration/invasion capabilities. Moreover, knockdown of IKKε suppressed cell proliferation. Cell cycle assay showed that the anti-proliferation effect of IKKε siRNA was mediated by arresting cells in the G0/G1 phase, which was caused by downregulation of cyclin D1. Furthermore, we demonstrated that silencing of IKKε inhibited the NF-κB basal activity as well as the Bcl-2 expression. Significant apoptosis was not observed in breast cancer cells upon the silencing of IKKε. The present study provided the first evidence that silencing IKKε using synthetic siRNA can inhibit the invasiveness properties and proliferation of breast cancer cells.

Conclusions

Our results suggested that silencing IKKε using synthetic siRNA may offer a novel therapeutic strategy for breast cancer.
Appendix
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Metadata
Title
Silencing of the IKKε gene by siRNA inhibits invasiveness and growth of breast cancer cells
Authors
Bin Qin
Kun Cheng
Publication date
01-10-2010
Publisher
BioMed Central
Published in
Breast Cancer Research / Issue 5/2010
Electronic ISSN: 1465-542X
DOI
https://doi.org/10.1186/bcr2644

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