Anti-Neoplastic Activity of Estrogen Receptor Beta in Chemoresistant Triple-Negative Breast Cancer

The standard of care for triple-negative breast cancer is chemotherapy followed by surgical resection, and in most cases, additional rounds of chemotherapy treatment. While highly effective, approximately half of patients will experience disease recurrence that does not respond to additional rounds of treatment. Previous findings demonstrate that estrogen receptor beta (ERb) is expressed in upwards of 20% of triple-negative tumors, and that ERb functions as a tumor suppressor in triple-negative breast cancer models, it was of interest to determine if the tumor-suppressive effects of ERb persisted in chemo-therapy-resistant forms of the disease. Here, we demonstrate that the activation of ERb in chemotherapy-resistant triple-negative breast cancer cell lines elicits equivalent or superior inhibitory effects compared to chemotherapy-sensitive counterparts. These findings support the potential use of ERb-targeting agents in advanced forms of the disease. Cells were plated in triplicate in charcoal-stripped FBS containing medium plus 100 ng/mL doxycycline to induce ERb expression. After 24 h, a medium change was performed containing either ethanol vehicle or 1nM E2. Triplicate for each treatment. Twenty-four hours post-treatment, total RNA was isolated and RNA seq was performed using an Illumina HiSeq 4000 platform.