Whereas the overexpression of PIAS1 has been shown to result in epigenetic silencing of breast cancer-associated genes, including ESR1 (ERα) [158], PIAS3 stimulates the proliferation of ER-positive breast cancer cells, and acts as a co-activator to regulate NR2E3-mediated activation of ESR1 expression [181,182], thus playing opposite roles in ERα regulation. The gene discussed is NR2E3; the disease is breast carcinoma.