{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T05:32:03Z","timestamp":1782970323326,"version":"3.54.5"},"reference-count":45,"publisher":"Wiley","issue":"18","license":[{"start":{"date-parts":[[2023,9,7]],"date-time":"2023-09-07T00:00:00Z","timestamp":1694044800000},"content-version":"vor","delay-in-days":6,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2023,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Oestrogen receptor alpha (ER) is involved in cell growth and proliferation and functions as a transcription factor, a transcriptional coregulator, and in cytoplasmic signalling. It affects, for example, bone, endometrium, ovaries and mammary epithelium. It is a key biomarker in clinical management of breast cancer, where it is used as a prognostic and treatment\u2010predictive factor, and a therapeutical target. Several ER isoforms have been described, but transcript annotation in public databases is incomplete and inconsistent, and functional differences are not well understood.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We have analysed short\u2010 and long\u2010read RNA sequencing data from breast tumours, breast cancer cell lines, and normal tissues to create a comprehensive annotation of ER transcripts and combined it with experimental studies of full\u2010length protein and six alternative isoforms.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The isoforms have varying transcription factor activity, subcellular localisation, and response to the ER\u2010targeting drugs tamoxifen and fulvestrant. Antibodies differ in ability to detect alternative isoforms, which raises concerns for the interpretation of ER\u2010status in routine pathology.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Future work should investigate the effects of alternative isoforms on patient survival and therapy response. An accurate annotation of ER isoforms will aid in interpretation of clinical data and inform functional studies to improve our understanding of the ER in health and disease.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cam4.6508","type":"journal-article","created":{"date-parts":[[2023,9,7]],"date-time":"2023-09-07T13:59:59Z","timestamp":1694095199000},"page":"18931-18945","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Alternative promoters and splicing create multiple functionally distinct isoforms of oestrogen receptor alpha in breast cancer and healthy tissues"],"prefix":"10.1002","volume":"12","author":[{"given":"Carlos Enrique","family":"Balcazar\u00a0Lopez","sequence":"first","affiliation":[{"name":"Department of Clinical Sciences Lund, Oncology Lund University Cancer Centre  Lund 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