Activation of the Estrogen Receptor-Alpha by Novel Anions

Abstract : The overall purpose of my project is to investigate the direct interaction of ER-alpha with eNOS and nitrite, and to determine what roles they might play in hormone independent breast cancers. I hope to characterize the interaction between ER-alpha and eNOS in the absence and presence of growth factors, determine whether polymorphic forms of eNOS increase ER-alpha activity due to increased nitrite production, and to determine the mechanism by which nitrite activates ER-alpha. Important findings to date have shown that treatment of wild-type ERalpha with nitrite leads to the dissociation of the hsp90 complex, binding to DNA, and the recruitment of the coactivator SRC-1 and RNA polymerase II to estrogen regulated gene promoters. These findings provide a novel role for nitrite in activation of ER-alpha.