The Role of Androgen Receptor as Biomarker in Triple Negative Breast Cancer

Abstract

Breast cancer is one of the most common diseases which is prevalent worldwide among women. Currently, there are three main markers that are Estrogen receptor (ER), Progesterone receptor (PR) and Human Epidermal Growth Factor Receptor-2 (HER-2). The presence of any of these three markers will help in deciding the therapeutic line of treatment for curing breast cancer. TNBC, a subtype of breast cancer, lacks the ER, PR, and HER2 expression. For such kinds of cancer, the options for treatment are fewer and the prognosis is poorer. However, a subtype of TNBC i.e., Luminal Androgen Receptor (LAR) has a significantly higher expression of Androgen receptor (AR) which can be targeted in order to inhibit the cell proliferation occurring as a result of activation of AR signaling pathway. AR-antagonists like Bicalutamide and Enzalutamide can be used against AR. In our current study, we wanted to analyse the inhibitory effects of AR antagonists on TNBC cells. Therefore, we performed cell viability (MTT) assays and examined the effect of drugs at different concentrations on cells at different time intervals ranging from 24, 48, and 72 hours. On performing the cell viability assay, the IC50 concentration of bicalutamide for cell line MDA-MB-453 was achieved 10.2 μM at time interval of 48 hrs. The IC50 concentration of bicalutamide for the MDA-MB-231 cell line was achieved 10.27 μM at the time interval of 24 hrs. The IC50 concentration of yet another AR antagonist Enzalutamide for the MDA- MB-231 cell line was achieved to be 37.20 μM at the time interval of 72 hrs. We also checked the effect of bicalutamide on the metastatic potential of MDA-MB-453 cells, cells were treated at the concentration of 10 μM and 20 μM for 24 hrs, it was observed that as the concentration increased, bicalutamide was able to inhibit the metastatic characteristics of the cells. Further, the gene expression of AR was checked by treating the MDA-MB-453 cells with 10 μM of bicalutamide, and significant downregulation of the gene was observed. However, no significant downregulation of AR-V7 which is a splice variant was observed. MDA-MB-231 cells were also treated with 10 μM bicalutamide nevertheless no significant downregulation of the AR as well as AR-V7 was observed.