RESUMO
BACKGROUND: Patients with cancer are at an increased risk of developing coagulation complications, and chemotherapy treatment increases the risk. Tumor progression is closely linked to the hemostatic system. Breast cancer tumors express coagulation factor V (FV), an essential factor in blood coagulation. The functional role of FV during treatment with chemotherapy is poorly understood and was explored in this study. OBJECTIVES: We aimed to investigate the role of FV in breast cancer progression by exploring associations with treatment response, gene regulation, and the functional effects of FV. METHODS: The receiver operating characteristic plotter was used to explore the predictive value of FV mRNA (F5) expression for treatment with FEC (5-fluorouracil, anthracycline, and cyclophosphamide). Breast cancer cohorts were analyzed to study treatment response to FEC. The effect of chemotherapy on F5 expression, the regulation of F5, and the functional effects of FV dependent and independent of chemotherapy were studied in breast cancer cell lines. RESULTS: F5 tumor expression was significantly higher in responders to FEC than in nonresponders. In vitro experiments revealed that anthracycline treatment increased the expression of F5. Inhibition and knockdown of p53 reduced the anthracycline-induced F5 expression. Mutation of a p53 half-site (c.158+1541/158+1564) in a luciferase plasmid reduced luciferase activity, suggesting that p53 plays a role in regulating F5. FV overexpression increased apoptosis and reduced proliferation slightly during anthracycline treatment. CONCLUSION: Our study identified F5 as a p53-regulated tumor suppressor candidate and a promising marker for response to chemotherapy. FV may have functional effects that are therapeutically relevant in breast cancer.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias da Mama , Ciclofosfamida , Fator V , Fluoruracila , Regulação Neoplásica da Expressão Gênica , Proteína Supressora de Tumor p53 , Humanos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Feminino , Proteína Supressora de Tumor p53/metabolismo , Proteína Supressora de Tumor p53/genética , Fluoruracila/uso terapêutico , Fluoruracila/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Ciclofosfamida/uso terapêutico , Fator V/genética , Fator V/metabolismo , Resultado do Tratamento , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Coagulação Sanguínea/efeitos dos fármacos , Células MCF-7 , Epirubicina/farmacologia , Epirubicina/uso terapêutico , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Mutação , RNA Mensageiro/metabolismo , RNA Mensageiro/genéticaRESUMO
Breast cancer (BCa) is a prevalent malignancy that predominantly affects women around the world. Somatic copy number alterations (CNAs) are tumor-specific amplifications or deletions of DNA segments that often drive BCa development and therapy resistance. Hence, the complex patterns of CNAs complement BCa classification systems. In addition, understanding the precise contributions of CNAs is essential for tailoring personalized treatment approaches. This review highlights how tumor evolution drives the acquisition of CNAs, which in turn shape the genomic landscapes of BCas. It also discusses advanced methodologies for identifying recurrent CNAs, studying CNAs in BCa and their clinical impact.