The presence of Estrogen Receptor β modulates the response of breast cancer cells to therapeutic agents

Breast cancer is a leading cause of death for women. The estrogen receptors (ERs) ratio is important in the maintenance of mitochondrial redox status, and higher levels of ER beta increases mitochondrial functionality, decreasing ROS production. Our aim was to determine the interaction between the ER alpha/ER beta ratio and the response to cytotoxic treatments such as cisplatin (CDDP), paclitaxel (PTX) and tamoxifen (TAM). Cell viability, apoptosis, autophagy, ROS production, mitochondrial membrane potential, mitochondrial mass and mitochondrial functionality were analyzed in MCF-7 (high ER alpha/ER beta ratio) and T47D (low ER alpha/ER beta ratio) breast cancer cell lines. Cell viability decreased more in MCF-7 when treated with CDDP and PTX.Apoptosis was less activated after cytotoxic treatments in T47D than in MCF-7 cells. Nevertheless, autophagy was increased more in CDDP-treated MCF-7, but less in TAM-treated cells than in T47D. CDDP treatment produced a raise in mitochondrial mass in MCF-7, as well as the citochrome c oxidase (COX) and ATP synthase protein levels, however significantly reduced COX activity. In CDDP-treated cells, the overexpression of ER beta in MCF-7 caused a reduction in apoptosis, autophagy and ROS production, leading to higher cell survival; and the silencing of ER beta in T47D cells promoted the opposite effects. In TAM-treated cells, ER beta-overexpression led to less cell viability by an increment in autophagy; and the partial knockdown of ER beta in T47D triggered an increase in ROS production and apoptosis, leading to cell death. In conclusion, ER beta expression plays an important role in the response of cancer cells to cytotoxic agents, especially for cisplatin treatment. (C) 2015 Elsevier Ltd. All rights reserved.