Author/Authors :
Wang، نويسنده , , Li Hua and Yang، نويسنده , , Xiao Yi and Zhang، نويسنده , , Xiaohu and An، نويسنده , , Ping and Kim، نويسنده , , Han-Jong and Huang، نويسنده , , Jiaqiang and Clarke، نويسنده , , Robert W.Osborne Jr.، نويسنده , , C. Kent and Inman، نويسنده , , John K. and Appella، نويسنده , , Ettore and Farrar، نويسنده , , William L.، نويسنده ,
Abstract :
Summary
ous obstacle to successful treatment of estrogen receptor (ER)-positive human breast cancer is cell resistance to tamoxifen (TAM) therapy. Here we show that the electrophile disulfide benzamide (DIBA), an ER zinc finger inhibitor, blocks ligand-dependent and -independent cell growth of TAM-resistant breast cancer in vitro and in vivo. Such inhibition depends on targeting disruption of the ER DNA-binding domain and its communication with neighboring functional domains, facilitating ERα dissociation from its coactivator AIB1 and concomitant association with its corepressor NCoR bound to chromatin. DIBA does not affect phosphorylation of HER2, MAPK, AKT, and AIB1, suggesting that DIBA-modified ERα may induce a switch from agonistic to antagonistic effects of TAM on resistant breast cancer cells.
