Abstract
BackgroundIKKε is an oncogenic kinase that was found amplified and overexpressed in a substantial percentage of human breast cancer cell lines and primary tumors using genomic and gene expression analyses. Molecular studies have provided the rational for a key implication of IKKε in breast cancer cells proliferation and invasiveness through the phosphorylation of several substrates.MethodsHere, we performed immunohistochemical detection of IKKε expression on tissue microarrays constituted of 154 characterized human breast cancer tumors. We further determined the association with multiple clinicopathological parameters and 5-years overall, disease-free and distant disease free survival.ResultsWe observed expression of IKKε in 60.4% of the breast cancer tumors. IKKε expression status showed no association with a panel of markers used for molecular classification of the tumors, including ER/PR/HER2 status, or with the molecular subtypes. However, IKKε expression was inversely associated with lymph node metastasis status (p = 0.0032). Additionally, we identified a novel association between IKKε and EGFR expression (p = 0.0011).ConclusionsThe unexpected observation of an inverse association between IKKε and lymph node metastasis advocates for larger scale immunohistochemical profiling of primary breast tumors to clarify the role of IKKε in metastasis. This study suggests that breast cancer tumors expressing EGFR and IKKε may be potential targets for drugs aiming at inhibiting IKKε activity or expression.
Highlights
IKKε is an oncogenic kinase that was found amplified and overexpressed in a substantial percentage of human breast cancer cell lines and primary tumors using genomic and gene expression analyses
Validation of anti-IKKε antibody To study the expression of IKKε at the protein level, the specificity of the commercially available monoclonal rabbit anti-IKKε D20G4 antibody used for tissue microarrays (TMA) IHC staining was first evaluated by immunoblot
Whole cell extracts (WCE) derived from the epithelial breast cancer cell line ZR75.1 transfected with control RNAi or RNAi designed to target IKKε
Summary
IKKε is an oncogenic kinase that was found amplified and overexpressed in a substantial percentage of human breast cancer cell lines and primary tumors using genomic and gene expression analyses. Molecular studies have provided the rational for a key implication of IKKε in breast cancer cells proliferation and invasiveness through the phosphorylation of several substrates. Suppression of IKKε by shRNA or transfection of a dominant negative form results in inhibition of anchorageindependent growth and invasiveness of breast cancer cell lines [13, 14]. In Triple Negative Breast Cancer cells (TNBC), IKKε is involved in the coordinated activation of NF-κB, STAT, and cytokine signaling [20]. Silencing of IKKε expression sensitizes ER+ T47D breast cancer cell line expressing high level of IKKε cells to Tam-induced cell death and apoptosis and to Tam-mediated inhibition of focus formation. Overexpression of IKKε protects the MCF-7 breast cancer cell line from Tam-induced cell death and apoptosis and reduced Tam-mediated inhibition of focus formation [21]
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