| Popis: |
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. |
