Activation of PERK/eIF2α/ATF4 signaling inhibits ERα expression in breast cancer.

ABSTRACT: Approximately 70-80% of breast cancers rely on estrogen receptor alpha (ERα) for growth. The unfolded protein response (UPR), a cellular response to endoplasmic reticulum stress (ERS), is an important process crucial for oncogenic transformation. The effect of ERS on ERα expression and signaling remains incompletely elucidated. Here, we focused on the regulatory mechanisms of ERS on ERα expression in ER-positive breast cancer (ER+ BC). Our results demonstrate that ERα protein and mRNA levels in ER+ BC cells are considerably reduced by the ERS inducers thapsigargin (TG) and brefeldin A (BFA) via the PERK/eIF2α/ATF4 signaling pathway. ChIP-qPCR and luciferase reporter gene analysis revealed that ERS induction facilitated ATF4 binding to the ESR1 (the gene encoding ERα) promoter region, there

SUBMITTER: Wu Y 

PROVIDER: S-EPMC12023901 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature