Consistent with E2-ERα activation of the anticipatory UPR, T47D breast cancer cells modified with CRISPR-Cas9 to replace wild-type ERα with the constitutively active mutations ERαY537S (TYS cells) and ERαD538G (TDG cells) upregulate the UPR in the absence of estrogen (13). Here, ESR1 is linked to breast carcinoma.