The natural L370F ERα variant confers endocrine resistance and sensitivity to ATRA in metastatic breast cancer cells.

ABSTRACT:

Background

Metastatic breast cancer (MBC) remains a major clinical challenge, particularly in estrogen receptor α (ERα)-positive patients who develop resistance to endocrine therapy (ET). While hotspot mutations such as Y537S in the ligand-binding domain (LBD) are well-characterized drivers of resistance, other ERα variants remain poorly studied. Understanding the molecular mechanisms underlying resistance in these variants is crucial for identifying novel therapeutic strategies. Here, we investigated the functional role of the L370F and E471D ERα variants, which are spatially close in the ERα structure.

Methods

Stable overexpressing HEK293 cells and CRISPR/CAS9 engineered MCF-7 cells were generated and treated with 17β-estradiol (E2), fulvestrant (Ful) and all-trans retinoi

SUBMITTER: Cipolletti M 

PROVIDER: S-EPMC12870731 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature