Apoptotic Action of 17-Estradiol in Raloxifene- Resistant MCF-7 Cells In Vitro and In Vivo

Background: Resistance to tamoxifen, a selective estrogen receptor modulator (SERM), involves changes that prevent apoptosis and enhance cell proliferation and survival. Para-doxically, estrogen treatment inhibits the growth of long-term tamoxifen-treated breast tumors. Because of the in-creasing use of raloxifene, another SERM, to prevent osteoporosis and potentially reduce breast cancer risk, some women will develop raloxifene-resistant breast cancer. We developed a raloxifene-resistant MCF-7 cell model (MCF-7/ Ral) and investigated the nature of raloxifene-resistant breast cancer and its response to estradiol. Methods: Ralox-ifene resistance and hormone responsiveness were assessed by proliferation assays and cell cycle analysis in parental MCF-7 and MCF-7/Ral cells. Nuclear factor B (NF-B) activity was investigated with a transient transfection assay