In the presence of 4OHT, while both pS2 and GREB1 were suppressed in parental, vector control and D151N COPS5-overexpressing cell lines, overexpression of WT COPS5 significantly increased the target gene expression (Fig. 2b, right four panels, Student's t-test P<0.01), indicating that overexpression of COPS5, depending on its catalytic activity, can convert the antagonistic 4OHT to an ERα agonist in breast cancer cells, a hallmark feature of endocrine-resistance at molecular level11. The gene discussed is ESR1; the disease is breast cancer.