LIGAND ACTIVATED ESTROGEN RECEPTOR BETA DISRUPTS METABOLIC REPROGRAMMING IN HUMAN SEMINOMA TCAM-2 CELLS

Abstract

Testicular germ cell tumors (TGCTs) represent the most common invasive malignant tumors inyoung male. The most widely accepted model of TGCTs development proposes a tumorigenic eventin utero followed by a dormancy period until puberty when TGCTs emerge, suggesting hormonalinvolvement and the estrogen-dependence of these tumors has been reported. Estrogens act throughestrogen receptors and human testis mainly express ERβ. ERβ loss is associated with advanced tumorstage, however the molecular mechanisms of the ERβ–protective effects are not defined yet. Recently,we showed that estradiol (E2) induced death in human testicular seminoma cells TCAM2 by a crosstalkbetween E2/ERa and the tumor suppressor gene PTEN, inducing autophagy and necroptosis. Cellsurvival is closely coupled to the cellular metabolism and tumor metabolism is considered a cancerhallmark and a novel target for cancer therapy. To further elucidate the role of ERβ in human seminomawe studied its effect on glucose and lipid metabolism in TCAM2 cells.