Detection of IKKε by immunohistochemistry in primary breast cancer: association with EGFR expression and absence of lymph node metastasis

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.

Molecular mechanism of gossypol mediating CCL2 and IL‑8 attenuation in triple‑negative breast cancer cells

“…Our current data supported these previous findings and interpreted the mechanism of ccl2 inhibition by GoSS. in TnBc cells, the IKBKE gene is expressed in 60% of BC tissue (74) and acts as an oncogene to support cell viability. Furthermore, the up-regulation of IKBKE enhances resistance to anticancer drugs and protects the Bc cells from Tamoxifen-induced apoptosis (75).…”

Sanguinarine Inhibition of TNF-α-Induced CCL2, IKBKE/NF-κB/ERK1/2 Signaling Pathway, and Cell Migration in Human Triple-Negative Breast Cancer Cells

“…Additionally, the simultaneous overexpression of CCL2 and IKBKE has been established by many studies [ 81 , 82 , 94 ]. In TNBC cells, the IKBKE oncogene is overexpressed in 60% of BC tissues [ 85 , 109 ]. In addition to its main function supporting BC cell viability, upregulated IKBKE increased resistance to antineoplastic therapy by eluding tamoxifen-promoted apoptosis [ 110 , 111 ].…”

“…In MDA-MB-231 cells, CCL2 gene silencing led to inhibition of CCL2 expression, which—in turn—led to the significant inhibition of tumor growth, cell proliferation, and increased necrosis [ 99 , 114 ]. Hence, the implication of IKBKE in breast carcinoma became a promising prospect for targeted therapies [ 109 ]. The current findings corroborate earlier research and suggest IKBKE repression as the anticipated mechanism of SANG-mediated CCL2 suppression [ 108 ].…”

Pharmacological inhibition of the IKKε/TBK-1 axis potentiates the anti-tumour and anti-metastatic effects of Docetaxel in mouse models of breast cancer

“…I B kinase subunit epsilon (IKK ), a key component of NF B signalling, has been identified as a breast cancer oncogene [6]. A number of studies have shown that IKK is overexpressed in mammary breast tumours and various human breast cancer cell lines [6,7], and its inhibition reduced the development of primary breast cancer in mice [8]. IKK has also been found to contribute to Tamoxifen resistance in oestrogen receptor positive (ER+) breast cancers [9].…”