MCF7-ESR1-Y537S-KI Cell Line

ESR1-Y537S is a clinically significant activating mutation in the estrogen receptor alpha (ERα) gene, arising from a tyrosine-to-serine substitution at codon 537 within the ligand-binding domain (LBD). This mutation confers ligand-independent constitutive activation of ERα, enabling persistent transcriptional activity and cell proliferation in the absence of estrogen. ESR1-Y537S is a hallmark of acquired resistance to endocrine therapies, including aromatase inhibitors and selective estrogen receptor degraders (SERDs) such as fulvestrant, and is frequently detected in metastatic breast cancer through liquid biopsy approaches. Mechanistically, the mutation stabilizes the active conformation of ERα, alters coregulator recruitment, and promotes chromatin remodeling, driving sustained oncogenic signaling. Preclinical models demonstrate that Y537S-mutant tumors exhibit aggressive phenotypes and evade standard endocrine therapies. Emerging therapeutic strategies include next-generation SERDs, selective estrogen receptor covalent antagonists (SERCAs), and proteolysis-targeting chimeras (PROTACs) designed to effectively degrade mutant ERα. ESR1-Y537S remains a critical biomarker for endocrine resistance and a key target for novel drug development.