GSE210092
Estrogen Receptor Beta 1: A Potential Therapeutic Target for Triple Negative Breast Cancer
Triple Negative Breast Cancer (TNBC) is an aggressive subtype of breast cancer characterized by the absence of estrogen receptor alpha, progesterone receptor, and human epidermal growth factor receptor 2 (HER2). These receptors are well characterized and often serve as targets in breast cancer treatment. As a result, TNBCs are difficult to treat and have a high propensity to metastasize to distant organs. For these reasons, TNBCs are responsible for over 50% of all breast cancer mortalities while only accounting for 15% - 20% of breast cancer cases. However, estrogen receptor beta 1 (ERß1) has emerged as a potential therapeutic target in the treatment of TNBCs. Using an in vivo xenograft preclinical mouse model with human TNBC, we found that expression of ERß1 significantly reduced both primary tumor growth and metastasis in the animals. Moreover, TNBCs with elevated levels of ERß1 showed reduction in epithelial-to-mesenchymal transition (EMT) markers and breast cancer stem cell (BCSC) markers, and increases in the expression of genes associated with inhibition of cancer cell invasiveness and metastasis, suggesting possible mechanisms underlying the antitumor activity of ERß1. Treatment with ERß1 agonist ligand often enhanced the suppressive activity of ERß1, suggesting their potential utility in improving TNBC treatment. The findings enable understanding of the mechanisms by which ERß impedes TNBC growth, invasiveness and metastasis and consideration of ways by which treatments involving ERß might improve TNBC patient outcome. Overall design: Examine how the presence of liganded and unliganded estrogen receptor beta isoform 1 influences gene expression, growth and metastasis of triple negative breast cancer cells.