ArticleOncogene2000
Cofactor competition between the ligand-bound oestrogen receptor and an intron 1 enhancer leads to oestrogen repression of ERBB2 expression in breast cancer.
Article in Oncogene, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
29 citing papers in PubMed, 1 synthesis or guideline pooled it, 109 citations in OpenAlex.
- Survival outcomes in HER2-low versus HER2-zero breast cancer after neoadjuvant chemotherapy: a meta-analysis.World journal of surgical oncology · 2024Pooled it
- A phase II trial to assess efficacy and safety of afatinib in extensively pretreated patients with HER2-negative metastatic breast cancer.Breast cancer research and treatment · 2012Trial
- Effects of short-course preoperative endocrine therapy on tumour morphology and immunohistochemical profile in oestrogen receptor-positive, HER2-negative breast cancer.Histopathology · 2026Article
- Association between Ancestry-Specific 6q25 Variants and Breast Cancer Subtypes in Peruvian Women.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2022Article
- Article
- Combination of mTORC1/2 inhibitor vistusertib plus fulvestrant in vitro and in vivo targets oestrogen receptor-positive endocrine-resistant breast cancer.Breast cancer research : BCR · 2019Article
- Targeting tumour re-wiring by triple blockade of mTORC1, epidermal growth factor, and oestrogen receptor signalling pathways in endocrine-resistant breast cancer.Breast cancer research : BCR · 2018Article
- Membrane-bound estrogen receptor alpha initiated signaling is dynamin dependent in breast cancer cells.European journal of medical research · 2018Article
- Regulation of HER2 oncogene transcription by a multifunctional coactivator/corepressor complex.Molecular endocrinology (Baltimore, Md.) · 2014Article
- Estrogen represses gene expression through reconfiguring chromatin structures.Nucleic acids research · 2013Article
- Bidirectional Crosstalk between the Estrogen Receptor and Human Epidermal Growth Factor Receptor 2 Signaling Pathways in Breast Cancer: Molecular Basis and Clinical Implications.Breast care (Basel, Switzerland) · 2013Review
- Inverse regulation of EGFR/HER1 and HER2-4 in normal and malignant human breast tissue.PloS one · 2013Article
- Steroid receptor coactivators, HER-2 and HER-3 expression is stimulated by tamoxifen treatment in DMBA-induced breast cancer.BMC cancer · 2012Article
- Clinical utility of the combination of lapatinib and letrozole in the management of hormone receptor-positive and HER2-positive advanced breast cancer.Breast cancer (Dove Medical Press) · 2011Review
- Oestrogen receptor-co-factor-chromatin specificity in the transcriptional regulation of breast cancer.The EMBO journal · 2011Article
- Fulvestrant-induced expression of ErbB3 and ErbB4 receptors sensitizes oestrogen receptor-positive breast cancer cells to heregulin β1.Breast cancer research : BCR · 2011Article
- Mechanisms of endocrine resistance in breast cancer.Annual review of medicine · 2011Review
- HER2: biology, detection, and clinical implications.Archives of pathology & laboratory medicine · 2011Review
- Breaking the cycle: An insight into the role of ERα in eukaryotic cell cycles.Journal of carcinogenesis · 2011Article
- Histone deacetylase 7 and FoxA1 in estrogen-mediated repression of RPRM.Molecular and cellular biology · 2010Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Overexpression of the ERBB2 proto-oncogene in breast tumours, which occurs in 25-30% of patients, correlates with poor prognosis. In oestrogen receptor (ER) positive breast epithelial cells oestrogens reduce ERBB2 mRNA and protein levels, an effect that is reversed in the presence of anti-oestrogens such as tamoxifen and ICI 182780. Our previous studies have shown that the major effect of oestrogen on ERBB2 expression is at the level of transcription and that this is mediated through a region within the ERBB2 first intron which can act as an oestrogen-suppressible enhancer in ER positive breast cells. In vitro footprinting of the smallest DNA fragment that retained full activity revealed four transcription factor binding sites. We report here that two of these sites are recognized by AP-2 proteins and the other two are bound by a variety of bZIP factors, including CREB and ATFI, with a major complex containing ATFa/ JunD. However, by using ER mutants it is clear that repression occurs essentially off the DNA. Indeed, the essential domain of the ER responsible for repression of the ERBB2 enhancer is a region termed AF2 which is required for the ligand-dependent association of non-DNA binding cofactors. We further demonstrate that one of these ER cofactors, SRC-1, can relieve oestrogen repression of the ERBB2 enhancer and conclude that these data fit with a model whereby the ER and the ERBB2 enhancer compete for this limiting, non-DNA binding cofactor. Thus, in oestrogenic conditions SRC-1 preferentially binds to the ER which effectively sequesters it thereby reducing enhancer activity, but in antioestrogenic media the cofactor is released from the ER and is therefore available to activate the ERBB2 enhancer.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.