However, dissection of these mechanisms of action is complicated by physical and functional interactions between ERα and SIRT1, where: (i) ERα is a SIRT1 substrate (Kim et al., 2006; Ji Yu et al., 2011), and (ii) SIRT1 functions as an ER coregulator required for the oncogenic effects of estrogens in breast cancer (Elangovan et al., 2011). The gene discussed is ESR1; the disease is breast cancer.