Mechanism of estrogen-induced apoptosis in breast cancer cells: Role of the NF-κB signaling pathway

摘要: The ability of sex steroid hormones to up-regulate the apoptotic signaling proteins is well documented; however, potential not remarkable and fully compensated by their growth stimulatory action target cells. In present study using long-term cultivation estrogen-dependent MCF-7 breast cancer cells in steroid-free medium, we have established a cell subline, designed as MCF-7/LS, which was characterized resistance estradiol hypersensitivity estrogen-induced apoptosis. We demonstrated that estrogen treatment does influence on level TNF-R1 or Fas, but dramatically decreases transcriptional activity NF-κB. Importantly, MCF-7/LS cells, are insensitive action, retain decrease NF-κB response stimulus. Furthermore, significant increase basal (in absence ligand) receptor (ER)-dependent revealed reciprocal antagonism between ER demonstrated. Finally, proved possible involvement phosphatidylinositol-3 kinase (PI3K) ligand-independent activation. general, results presented suggest medium accompanied with ER-dependent maintenance negative regulatory loop ER-NF-κB. latter may be considered one factors resulting disbalance pro-and anti-apoptotic pathways enhancement