Estrogen Receptor Beta (Erβ) Maintains Mitochondrial Network Regulating Invasiveness in an Obesity-Related Inflammation Condition in Breast Cancer

Abstract

Obesity, a physiological situation where different proinflammatory cytokines and hormones are secreted, is a major risk factor for breast cancer. Mitochondrial functionality exhibits a relevant role in the tumorigenic potential of a cancer cell. In the present study, it has been examined the influence of an obesity-related inflammation ELIT treatment (17 beta-estradiol, leptin, IL-6, and TNF alpha), which aims to stimulate the hormonal conditions of a postmenopausal obese woman on the mitochondrial functionality and invasiveness of MCF7 and T47D breast cancer cell lines, which display a different ratio of both estrogen receptor isoforms, ER alpha and ER beta. The results showed a decrease in mitochondrial functionality, with an increase in oxidative stress and invasiveness and motility, in the MCF7 cell line (high ER alpha/ER beta ratio) compared to a maintained status in the T47D cell line (low ER alpha/ER beta ratio) after ELIT treatment. In addition, breast cancer biopsies were analyzed, showing that breast tumors of obese patients present a high positive correlation between IL-6 receptor and ER beta and have an increased expression of cytokines, antioxidant enzymes, and mitochondrial biogenesis and dynamics genes. Altogether, giving special importance to ER beta in the pathology of obese patients with breast cancer is necessary, approaching to personalized medicine.