Progesterone receptors drive advanced breast cancer phenotypes including circulating tumor- and stem-like cell expansion in the context of <i>ESR1</i> mutation.

ABSTRACT: Endocrine therapy resistance remains a major challenge in the treatment of advanced estrogen receptor positive (ER+) breast cancer. This can be driven by acquired mutations in the estrogen receptor gene (ESR1), such as Y537S or D538G, that primarily emerge in patients with prior aromatase inhibitor therapy and results in constitutive estrogen-independent ER activity. Progesterone receptors (PR) are important modifiers of ER activity, in part via direct binding. We previously showed that PR mediates expansion of cancer stem-like cell (CSC) populations and promotes tamoxifen resistance in nuclear ER/PR transcriptional complexes. In this study, we sought to define whether PR function changes in the context of ESR1 mutations. PR readily interacted with wild type (WT), but not Y53

SUBMITTER: Truong TH 

PROVIDER: S-EPMC12668012 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature