Abstract
BackgroundBRK is, a non-receptor tyrosine kinase, overexpressed in approximately 85% of human invasive ductal breast tumors. It is not clear whether BRK expression correlates with breast cancer subtypes, or the expression has prognostic or diagnostic significance. Herein, we investigated the correlation of BRK with any breast cancer subtypes and clinicopathological significance of BRK expression in breast cancer.MethodsIn this study, we examined BRK expression in 120 breast tumor samples and 29 breast cancer cell lines to explore the positive correlation between BRK and the expression of ERα. We used immunohistochemistry, RT-PCR, and immunoblotting to analyse our experimental samples.ResultWe demonstrate that estrogen induces BRK gene and protein expression in ER+ breast cancer cells. Over-expression of ERα in the ER-negative breast cancer cell line increased BRK expression, and knock-down of ESR1 in MCF7 cells reduced BRK levels. Further, we provide evidence that BRK is regulated by ERα signaling and the presence of ER antagonists (tamoxifen and fulvestrant) reduce the expression of BRK in ER-positive breast cancer cells. Finally, we demonstrate that the overall survival of ER-positive breast cancer patients is poor when their cancers express high levels of BRK.ConclusionOur data indicate that BRK is a prognostic marker for ER+ breast cancers and provide a strong rationale for targeting BRK to improve patients’ survival.
Highlights
Breast Tumor Kinase (BRK) is, a non-receptor tyrosine kinase, overexpressed in approximately 85% of human invasive ductal breast tumors
We observed that BRK mRNA expression was higher in most of the cancers compared to the non-cancerous tissues (Fig. 1a)
Our findings indicate that BRK mRNA is upregulated in most cancers, but the differential expression of BRK is most significant in breast cancer as compared to normal tissues
Summary
BRK is, a non-receptor tyrosine kinase, overexpressed in approximately 85% of human invasive ductal breast tumors. It is not clear whether BRK expression correlates with breast cancer subtypes, or the expression has prognostic or diagnostic significance. Breast tumors are classified into four major molecular subtypes [1,2,3]: HER2 (human epidermal growth factor receptor 2) type, Basal cell type, and Luminal A and B types. The Basal cell type is mostly characterized as triple-negative breast cancer (TNBC) because of the lack of ER and progesterone receptor (PR) expression and HER2 amplification. No investigation has been undertaken to explore whether the overexpression of BRK is linked with any of these major subtypes
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