To further evaluate the role of COPS5 in a model system, we attempted to establish in vitro models derived from MCF7 ERα+ breast cancer cells that are highly resistant to 4-hydroxy-tamoxifen (4OHT, an active metabolite of tamoxifen) at up to 2 μM by a dose-escalation protocol (refer to Methods) (Fig. 1f). Here, ESR1 is linked to breast cancer.