{"entity": "publication", "iuid": "3dbf25258023458fa9d97168e2735509", "timestamp": "2026-08-22T06:56:34.222Z", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/3dbf25258023458fa9d97168e2735509.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/3dbf25258023458fa9d97168e2735509"}}, "title": "ER\u03b1 and ER\u03b2 Homodimers in the Same Cellular Context Regulate Distinct Transcriptomes and Functions.", "authors": [{"family": "Song", "given": "Dandan", "initials": "D"}, {"family": "He", "given": "Huan", "initials": "H"}, {"family": "Indukuri", "given": "Rajitha", "initials": "R"}, {"family": "Huang", "given": "Zhiqiang", "initials": "Z"}, {"family": "Stepanauskaite", "given": "Lina", "initials": "L"}, {"family": "Sinha", "given": "Indranil", "initials": "I"}, {"family": "Haldos\u00e9n", "given": "Lars-Arne", "initials": "LA"}, {"family": "Zhao", "given": "Chunyan", "initials": "C"}, {"family": "Williams", "given": "Cecilia", "initials": "C"}], "type": "journal article", "published": "2022-07-06", "journal": {"title": "Front Endocrinol (Lausanne)", "issn": "1664-2392", "volume": "13", "pages": "930227", "issn-l": "1664-2392"}, "abstract": "The two estrogen receptors ER\u03b1 and ER\u03b2 are nuclear receptors that bind estrogen (E2) and function as ligand-inducible transcription factors. They are homologues and can form dimers with each other and bind to the same estrogen-response element motifs in the DNA. ER\u03b1 drives breast cancer growth whereas ER\u03b2 has been reported to be anti-proliferative. However, they are rarely expressed in the same cells, and it is not fully investigated to which extent their functions are different because of inherent differences or because of different cellular context. To dissect their similarities and differences, we here generated a novel estrogen-dependent cell model where ER\u03b1 homodimers can be directly compared to ER\u03b2 homodimers within the identical cellular context. By using CRISPR-cas9 to delete ER\u03b1 in breast cancer MCF7 cells with Tet-Off-inducible ER\u03b2 expression, we generated MCF7 cells that express ER\u03b2 but not ER\u03b1. MCF7 (ER\u03b2 only) cells exhibited regulation of estrogen-responsive targets in a ligand-dependent manner. We demonstrated that either ER was required for MCF7 proliferation, but while E2 increased proliferation via ER\u03b1, it reduced proliferation through a G2/M arrest via ER\u03b2. The two ERs also impacted migration differently. In absence of ligand, ER\u03b2 increased migration, but upon E2 treatment, ER\u03b2 reduced migration. E2 via ER\u03b1, on the other hand, had no significant impact on migration. RNA sequencing revealed that E2 regulated a transcriptome of around 800 genes via each receptor, but over half were specific for either ER\u03b1 or ER\u03b2 (417 and 503 genes, respectively). Functional gene ontology enrichment analysis reinforced that E2 regulated cell proliferation in opposite directions depending on the ER, and that ER\u03b2 specifically impacted extracellular matrix organization. We corroborated that ER\u03b2 bound to cis-regulatory chromatin of its unique proposed migration-related direct targets ANXA9 and TFAP2C. In conclusion, we demonstrate that within the same cellular context, the two ERs regulate cell proliferation in the opposite manner, impact migration differently, and each receptor also regulates a distinct set of target genes in response to E2. The developed cell model provides a novel and valuable resource to further complement the mechanistic understanding of the two different ER isoforms.", "doi": "10.3389/fendo.2022.930227", "pmid": "35872983", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC9299245"}], "notes": [], "created": "2026-08-21T12:58:13.957Z", "modified": "2026-08-21T12:58:13.986Z"}