biostudies-literatureHuggins RJU.S. Department of Health & Human Services | NIH | National Cancer InstituteVirginia and D.K. Ludwig Fund for Cancer ResearchNCI NIH HHS96https://www.ebi.ac.uk/biostudies/studies/S-EPMC10689488biostudies-literatureUnknown9(1)The constitutively active ESR1 Y537S mutation is associated with endocrine therapy (ET) resistance and progression of metastatic breast cancer through its effects on estrogen receptor (ERα) gene regulatory functions. However, the complex relationship between ERα and the progesterone receptor (PR), known as ERα/PR crosstalk, has yet to be characterized in the context of the ERα Y537S mutation. Using proximity ligation assays, we identify an increased physical interaction of ERα and PR in the context of the ERα Y537S mutation, including in the nucleus where this interaction may translate to altered gene expression. As such, more than 30 genes were differentially expressed in both patient tumor and cell line data (MCF7 and/or T47D cells) in the context of the ERα Y537S mutation compared to ERNPJ breast cancerERα/PR crosstalk is altered in the context of the ERα Y537S mutation and contributes to endocrine therapy-resistant tumor proliferation.PMC106894885F31CA257634-02F31 CA257634T32 CA009594Huggins RJGreene GLfalseERα/PR crosstalk is altered in the context of the ERα Y537S mutation and contributes to endocrine therapy-resistant tumor proliferation.The constitutively active ESR1 Y537S mutation is associated with endocrine therapy (ET) resistance and progression of metastatic breast cancer through its effects on estrogen receptor (ERα) gene regulatory functions. However, the complex relationship between ERα and the progesterone receptor (PR), known as ERα/PR crosstalk, has yet to be characterized in the context of the ERα Y537S mutation. Using proximity ligation assays, we identify an increased physical interaction of ERα and PR in the context of the ERα Y537S mutation, including in the nucleus where this interaction may translate to altered gene expression. As such, more than 30 genes were differentially expressed in both patient tumor and cell line data (MCF7 and/or T47D cells) in the context of the ERα Y537S mutation compared to ER2023-01-01T00:00:00Z2023 Nov2026-07-15T00:35:09.736Z2025-04-04T09:39:50.717ZS-EPMC106894883803654610.1038/s41523-023-00601-7