ArticleMolecular and cellular biology2011
Hypoxia-inducible factor 1 is activated by dysregulated cyclin E during mammary epithelial morphogenesis.
Article in Molecular and cellular biology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02160730 (Treatment of Pituitary Cushing Disease With a Selective CDK Inhibitor, R-roscovitine), which is not on this map. Cited by 15 papers.
What it found
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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.
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.
Treatment of Pituitary Cushing Disease With a Selective CDK Inhibitor, R-roscovitine
Who cites it
15 citing papers in PubMed, 17 citations in OpenAlex.
- Dietary walnut altered gene expressions related to tumor growth, survival, and metastasis in breast cancer patients: a pilot clinical trial.Nutrition research (New York, N.Y.) · 2019Trial
- Conservation of Long G4-rich (LG4) genomic enhancer regulations.BMC genomics · 2026Article
- Spatial and single-cell transcriptomics reveal a HIF-1α/NF-κB-driven hypoxia-induced senescence axis in BPH epithelium.International journal of biological sciences · 2026Article
- Integrated DNA Methylation and Transcriptome Analysis Reveals Epigenetic Mechanisms of Lactation Performance Differences in Cloned Buffalo.International journal of molecular sciences · 2025Article
- Foxp1 suppresses cortical angiogenesis and attenuates HIF-1alpha signaling to promote neural progenitor cell maintenance.EMBO reports · 2024Article
- EEF1A2 promotes HIF1A mediated breast cancer angiogenesis in normoxia and participates in a positive feedback loop with HIF1A in hypoxia.British journal of cancer · 2024Article
- Regulation of hypoxia-inducible factor functions in the nucleus by sphingosine-1-phosphate.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020Article
- Article
- Regulation of cell proliferation by hypoxia-inducible factors.American journal of physiology. Cell physiology · 2015Review
- Cell cycle progression in response to oxygen levels.Cellular and molecular life sciences : CMLS · 2014Review
- Article
- Opiorphin is a master regulator of the hypoxic response in corporal smooth muscle cells.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2014Article
- Mathematical model of a telomerase transcriptional regulatory network developed by cell-based screening: analysis of inhibitor effects and telomerase expression mechanisms.PLoS computational biology · 2014Article
- Hyper-mitogenic drive coexists with mitotic incompetence in senescent cells.Cell cycle (Georgetown, Tex.) · 2012Article
- An integrated view of cyclin E function and regulation.Cell cycle (Georgetown, Tex.) · 2012Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
Increased cyclin E expression has been identified in human tumors of diverse histologies, and in studies of primary breast cancers, high cyclin E is associated with poor prognosis. We have studied dysregulated cyclin E in epithelial tissues using organotypic cultures of human mammary epithelial cells and a murine model. We unexpectedly discovered that dysregulated cyclin E impairs normal acinar morphogenesis in vitro, and this is associated with the induction of p21(Cip1), p27(Kip1), and cellular senescence. Cyclin E-induced morphogenesis arrest is dependent upon hypoxia-inducible factor 1α (HIF-1α), which itself is induced by high cyclin E both in cultured mammary acini and in mammary epithelial tissues in a mouse model of deregulated cyclin E expression. We next determined that E2F activity directly regulates and is required for induction of HIF1A by cyclin E. Additionally, we found that cyclin E deregulation in mammary acini decreases, in an E2F-independent manner, expression of the EGLN1 prolyl hydroxylase that regulates HIF-1α degradation within the VHL ubiquitin ligase pathway. Together, our findings reveal a direct link between cyclin E and HIF-1 activities in mammary epithelial cells and implicate HIF-1 as a mediator of proliferation-independent phenotypes associated with high cyclin E expression in some human breast cancers.
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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.