Discovery of naturally occurring ESR1 mutations in breast cancer cell lines modelling endocrine resistance.

ABSTRACT: Resistance to endocrine therapy remains a major clinical problem in breast cancer. Genetic studies highlight the potential role of estrogen receptor-α (ESR1) mutations, which show increased prevalence in the metastatic, endocrine-resistant setting. No naturally occurring ESR1 mutations have been reported in in vitro models of BC either before or after the acquisition of endocrine resistance making functional consequences difficult to study. We report the first discovery of naturally occurring ESR1 ^Y537C and ESR1 ^Y537S mutations in MCF7 and SUM44 ESR1-positive cell lines after acquisition of resistance to long-term-estrogen-deprivation (LTED) and subsequent resistance to fulvestrant (ICIR). Mutations were enriched with time, impacted on ESR1 binding to the genome and a

SUBMITTER: Martin LA 

PROVIDER: S-EPMC5709387 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature