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 hor-mones 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 exam-ined the influence of an obesity-related inflammation ELIT treatment (17β-estradiol, leptin, IL-6, and TNFα), 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, ERα and ERβ. The results showed a decrease in mitochondrial functionality, with an increase in oxidative stress and inva-siveness and motility, in the MCF7 cell line (high ERα/ERβ ratio) compared to a maintained status in the T47D cell line (low ERα/ERβ 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 ERβ and have an increased expression of cytokines, antioxidant en-zymes, and mitochondrial biogenesis and dynamics genes. Altogether, giving special importance to ERβ in the pathology of obese patients with breast cancer is necessary, approaching to person-alized medicine.