ArticleOncotarget2016
Estrogen-dependent downregulation of hypoxia-inducible factor (HIF)-2α in invasive breast cancer cells.
Article in Oncotarget, 2016. 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 17 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
17 citing papers in PubMed, 22 citations in OpenAlex.
- Hormonal status and reproductive life-course states as modulators of women's physiological responses to acute and chronic hypoxia: insights, challenges, and perspectives.Biology of sex differences · 2026Review
- Ferroptosis-related gene EPAS1 suppresses breast cancer progression by inhibiting M2 macrophage polarization.Discover oncology · 2026Article
- Article
- Inherent single-cell heterogeneity of the transcriptional response to hypoxia in cancer cells.NAR cancer · 2025Article
- Cognitive Impairment Mechanisms in High-Altitude Exposure: Proteomic and Metabolomic Insights.Journal of proteome research · 2024Article
- Patient Sex and Origin Influence Distribution of Driver Genes and Clinical Presentation of Paraganglioma.Journal of the Endocrine Society · 2024Article
- The Role of Hypoxia-Inducible Factor Isoforms in Breast Cancer and Perspectives on Their Inhibition in Therapy.Cancers · 2022Review
- Multifaceted Interplay between Hormones, Growth Factors and Hypoxia in the Tumor Microenvironment.Cancers · 2022Review
- Hypoxia inducible factors regulate hepatitis B virus replication by activating the basal core promoter.Journal of hepatology · 2021Article
- Protective role of estrogen against excessive erythrocytosis in Monge's disease.Experimental & molecular medicine · 2021Article
- Article
- HIFs, angiogenesis, and metabolism: elusive enemies in breast cancer.The Journal of clinical investigation · 2020Review
- HIF-2α regulates CD44 to promote cancer stem cell activation in triple-negative breast cancerWorld journal of stem cells · 2020Article
- Article
- Inherent DNA-binding specificities of the HIF-1α and HIF-2α transcription factors in chromatin.EMBO reports · 2019Article
- Crosstalk between Notch, HIF-1α and GPER in Breast Cancer EMT.International journal of molecular sciences · 2018Review
- Prognostic Role of Hypoxia-Inducible Factor-2α Tumor Cell Expression in Cancer Patients: A Meta-Analysis.Frontiers in oncology · 2018Article
Corrections and comments
- Erratum issued
Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The involvement of estrogen (E2) and hypoxia in tumor progression is well established. Hypoxia has been reported to activate and degrade estrogen receptor alpha (ERα) in breast cancer cells. Furthermore, E2 has been shown to regulate hypoxia-inducible factor (HIF)-1α protein, but its role in HIF-2α regulation remains largely unexplored. In this study, we found that both HIF-2α mRNA and protein were down-regulated in ER positive but not ER negative breast cancer cells upon treatment with E2. The analysis of 690 samples derived from 608 mixed and 82 triple-negative breast cancer patients revealed that high nuclear HIF-2α tumor levels are associated with a worse prognosis specifically in human epidermal growth factor receptor 2 (HER2) and hormone receptor positive patients. Consistently, ERα/HER2 positive breast cancer cells displayed less pronounced downregulation of HIF-2α by E2. Experiments using a histone deacetylase inhibitor indicate that the E2 mediated decrease in HIF-2α mRNA is due to transcriptional repression. A functional estrogen response element (ERE) was identified in the first intron of the gene encoding HIF-2α (EPAS1), suggesting transcriptional co-repressor recruitment by ERα. Our results demonstrate a novel modulation of HIF-2α in breast cancer cells, explaining the opposing regulation between HIF-1α and HIF-2α in hormone-responsive breast cancer.
Indexed as
Identifiers
What OpenQuestion holds
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.