ArticleCancer medicine2023
Alternative promoters and splicing create multiple functionally distinct isoforms of oestrogen receptor alpha in breast cancer and healthy tissues.
Article in Cancer medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed.
- Exon 7 splicing of ERα predicts poor prognosis and increases phenotypic heterogeneity in luminal a subtype breast cancer.FEBS open bio · 2026Article
- ChIP happens: from biochemical origins to the modern omics toolbox for understanding steroid hormone receptors.The Biochemical journal · 2026Review
- Dynamic methylation and expression of alternative promoters for oestrogen receptor alpha in cell line models of fulvestrant resistance.Molecular oncology · 2025Article
- Isoform-level expression of the constitutive androstane receptor (CAR or NR1I3) transcription factor better predicts the mRNA expression of the cytochrome P450s in human liver samples.Drug metabolism and disposition: the biological fate of chemicals · 2025Article
- Alternative promoters and splicing create multiple functionally distinct isoforms of oestrogen receptor alpha in breast cancer and healthy tissues.Cancer medicine · 2023Article
Corrections and comments
- Erratum issued
Authors and funding
7 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundOestrogen 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-predictive 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.
methodsWe have analysed short- and long-read 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-length protein and six alternative isoforms.
resultsThe isoforms have varying transcription factor activity, subcellular localisation, and response to the ER-targeting drugs tamoxifen and fulvestrant. Antibodies differ in ability to detect alternative isoforms, which raises concerns for the interpretation of ER-status in routine pathology.
conclusionsFuture 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.
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