NF-?? Pathway is a key modulator of BRCA-1 mutation induced chemo-Resistance in triple negative breast cancer

Jeyakumar Balakrishnan, Ambujam Govindasamy, Arunagiri Ramuthevar, Suganya Kannan

Department of Surgery, Vinayaka Mission’s Medical College and Hospital (Vinayaka Mission Research Foundation, Karaikal, Puducherry, India

ABSTRACT

Triple-negative breast cancer (TNBC) is considered to be more aggressive and have a poorer prognosis than other types of breast cancer. The specific gene expression pattern between TNBC and other non-triple negative breast cancer (nTNBC) is yet to be resolved. Hence the present study was aimed to study the BRCA-1 status and measure the important tumor markers mRNA expression in peripheral blood samples of TNBC and other nTNBC subjects and compared with control subjects. EDTA blood samples were obtained from 25 CA (cancer) breast patients and 25 controls for DNA and RNA isolation. PCR-RFLP analysis was performed to check the BRCA-1 mutation in all the samples. Results showed that BRCA-1 mutation was present in all TNBC patients. Subsequently, quantitative RT-PCR was performed to detect the relative mRNA expression of NF-κβ, VEGFA, Caspase-3, and ERBB2 gene transcripts. Results showed that the transcript levels of NF-κβ, VEGFA, and ERBB2 were significantly up regulated in TNBC (p=0.0001) when compared to nTNBC and control. Transcript levels of caspase-3 were significantly down regulated (p=0.0001) in TNBC compared to nTNBC and control subjects. In conclusion, BRCA-1 mutation in TNBC patients confers resistance to chemotherapy activated by NF-κβ pathway and activation of adhesion and angiogenesis was associated with aggressive and poor prognosis in TNBC patients.

Keywords:

TNBC, Breast cancer, Cytokines, Tumour and gene expression.