Title:
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The identification and characterisation of TBXA2R as an oncogenic driver in triple negative breast cancer
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Triple Negative Breast Cancer (TNBC) is defined by the lack of ERa, PR and normal HER2 receptor expression.
The majority ofTNBCs are also basal-like breast cancers (BLBCs) which express basal cytokeratins found in the
normal basal epithelia of the breast. BRCA 1 mutant breast cancers closely resemble the TNBC/BLBC subtypes
and BRCA 1 expression is down-regulated in approximately 30% of sporadic invasive BLBCs. Unlike luminal
or HER2-positive breast cancers, there are no specific therapies available for TNBC as they lack targetable
receptors, and therefore have a poor clinical outcome. Our aim was to identify genes involved in pathogenic
events driving TNBC proliferation which could represent novel therapeutic targets. We have performed
microarray profiling of 16 primary TNBCs (8 good and 8 poor FEC outcome). Elevated levels of the
thromboxane A2 receptor gene (TBXA2R) were observed in good outcome TNBCs, and triplicate siRNA
knockdowns ofTBXA2R showed dramatic growth inhibition in TNBC/BLBC cell lines but not in 'normal'
HME-1 basal cells indicating specificity for BLBC. TBXA2R is a G-protein coupled receptor with a wellestablished
role in platelet activation and haemostasis and is known to regulate diverse cellular processes such as
angiogenesis, cell survival and cytoskeletal arrangement.
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