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Updated: Mar 16, 2026

A Method to Study the C924T Polymorphism of the Thromboxane A2 Receptor Gene
Published on: April 1, 2019
Thromboxane A2 receptor (TBXA2R) is a potent survival factor for triple negative breast cancers (TNBCs)
Katy Orr1, Niamh E Buckley1, Paula Haddock1
1Centre for Cancer Research and Cell Biology, Queen's University Belfast, Belfast, UK.
Abstract:
Triple Negative Breast Cancer (TNBC) is defined by the lack of ERα, PR expression and HER2 overexpression and is the breast cancer subtype with the poorest clinical outcomes. Our aim was to identify genes driving TNBC proliferation and/or survival which could represent novel therapeutic targets.We performed microarray profiling of primary TNBCs and generated differential genelists based on clinical outcomes following the chemotherapy regimen FEC (5-Fluorouracil/Epirubicin/Cyclophosphamide -'good' outcome no relapse > 3 years; 'poor' outcome relapse < 3 years). Elevated expression of thromboxane A2 receptor (TBXA2R) was observed in 'good' outcome TNBCs. TBXA2R expression was higher specifically in TNBC cell lines and TBXA2R knockdowns consistently showed dramatic cell killing in TNBC cells. TBXA2R mRNA and promoter activities were up-regulated following BRCA1 knockdown, with c-Myc being required for BRCA1-mediated transcriptional repression.We demonstrated that TBXA2R enhanced TNBC cell migration, invasion and activated Rho signalling, phenotypes which could be reversed using Rho-associated Kinase (ROCK) inhibitors. TBXA2R also protected TNBC cells from DNA damage by negatively regulating reactive oxygen species levels. In summary, TBXA2R is a novel breast cancer-associated gene required for the survival and migratory behaviour of a subset of TNBCs and could provide opportunities to develop novel, more effective treatments.
Insights
Thromboxane A2 receptor (TBXA2R) is elevated in good-outcome Triple Negative Breast Cancer (TNBC). Targeting TBXA2R shows promise for treating TNBC by inhibiting cell survival and migration.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Triple Negative Breast Cancer (TNBC) presents the poorest clinical outcomes among breast cancer subtypes.
- TNBC is characterized by the absence of Estrogen Receptor alpha (ERα), Progesterone Receptor (PR), and Human Epidermal growth factor Receptor 2 (HER2) expression.
- Identifying novel therapeutic targets is crucial for improving TNBC patient prognosis.
Purpose of the Study:
- To identify genes that drive proliferation and/or survival in TNBC.
- To discover potential novel therapeutic targets for TNBC treatment.
Main Methods:
- Microarray profiling of primary TNBC samples.
- Differential gene expression analysis based on clinical outcomes (relapse within 3 years vs. no relapse > 3 years) after FEC chemotherapy.
- Investigated the role of Thromboxane A2 receptor (TBXA2R) in TNBC cell lines, including knockdown experiments and analysis of its regulation by BRCA1 and c-Myc.
Main Results:
- Elevated TBXA2R expression was observed in TNBCs with a good clinical outcome.
- TBXA2R knockdown led to significant cell killing in TNBC cell lines.
- TBXA2R expression is upregulated by BRCA1 knockdown, with c-Myc mediating this transcriptional repression.
- TBXA2R promotes TNBC cell migration, invasion, and activates Rho signaling, which can be inhibited by ROCK inhibitors.
- TBXA2R confers resistance to DNA damage by reducing reactive oxygen species levels.
Conclusions:
- TBXA2R is a novel gene associated with breast cancer, essential for the survival and migration of a subset of TNBC.
- TBXA2R represents a potential therapeutic target for developing more effective treatments for Triple Negative Breast Cancer.
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