Regulation of mineralocorticoid receptor and its downstream targets by estrogen and aldosterone in breast cancer

Abstract

Many women suffer from breast cancer worldwide thus accurate diagnosis of this disease has become an important issue for treatment options and improved clinical outcomes. Members of steroid hormone receptors, are a subfamily of nuclear receptors can serve as biomarkers in molecular classification of breast cancer. One of these, Mineralocorticoid Receptor (MR) takes part in many physiological processes in epithelial tissues including mammary epithelia, yet it is not well studied in the context of breast cancer. In this thesis, we investigated expression patterns of MR together with Glucocorticoid Receptor (GR) across multiple breast cancer cell lines at the protein level. Our study revealed that expressions of MR and GR were modulated in breast cancer as a subtype specific manner. We then enquired regulation of MR and its downstream targets, SGK1, NEDD4-2 and subunits of ENaC i.e., α, β and γ, by estrogen (E2) and aldosterone (ALDO) treatment in breast cancer via qPCR and Western Blotting. We found differential responses in expression of MR and its downstream targets to E2 and ALDO suggesting ER status was an important mediator of MR action. We also overexpressed MR in MCF7 cells and then showed that MR, NEDD4-2, β and γENaC mRNA levels increased in response to ALDO only when MR was overexpressed.