HIF‐1α is required for solid tumor formation and embryonic vascularization
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The transcriptional response to lowered oxygen levels is mediated by the hypoxia-inducible transcription factor (HIF-1), a heterodimer consisting of the constitutively expressed aryl hydrocarbon receptor nuclear translocator (ARNT) and the hypoxic response factor HIF-1alpha. To study the role of the transcriptional hypoxic response in vivo we have targeted the murine HIF-1alpha gene. Loss of HIF-1alpha in embryonic stem (ES) cells dramatically retards solid tumor growth; this is correlated with a reduced capacity to release the angiogenic factor vascular endothelial growth factor (VEGF) during hypoxia. HIF-1alpha null mutant embryos exhibit clear morphological differences by embryonic day (E) 8.0, and by E8.5 there is a complete lack of cephalic vascularization, a reduction in the number of somites, abnormal neural fold formation and a greatly increased degree of hypoxia (measured by the nitroimidazole EF5). These data demonstrate the essential role of HIF-1alpha in controlling both embryonic and tumorigenic responses to variations in microenvironmental oxygenation.
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Vascularization is severely impaired in HIF1A-/- and HIF2A-/- mice.
“Vascularization is severely impaired in HIF1A -/- (Carmeliet et al., 1998;Ryan et al., 1998) and HIF2A -/- (Peng et al., 2000) mice.”
From Therapeutic targeting of hypoxia and hypoxia-inducible factors in cancer (2016) · cites this paper as Ryan et al., 1998
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- Authors
- Ryan, H. E., Lo, J., & Johnson, R. S.
- Affiliations
- University of California San Diego (US)
- Corresponding author
- Johnson, Randall S.
- Venue
- The EMBO Journal
- Published
- 1998-06-01
- Volume
- 17
- Issue
- 11
- Pages
- 3005-3015
- ISSN
- 0261-4189 (ISSN-L)
- 1460-2075
- PMC
- PMC1170640
- OpenAlex
- W2109492293
- Cited by
- 1,579
- References
- 3
- Citations by year
- 2026: 6 · 2025: 14 · 2024: 27 · 2023: 28 · 2022: 38 · 2021: 37 · 2020: 40 · 2019: 31 · 2018: 38 · 2017: 35 · 2016: 40 · 2015: 53 · 2014: 58 · 2013: 71 · 2012: 57
- FWCI
- 22.84
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The EMBO Journal (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- University of California, San Diego
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Kruppel-like factors research
- Keywords
- HIF-1α, hypoxia-inducible factor, hypoxia, tumor angiogenesis, vascular endothelial growth factor, embryonic stem cells, somite development, oxygenation, ARNT
- MeSH terms
- Animals, DNA-Binding Proteins, Embryo, Mammalian, Gene Expression Regulation, Head, Male, Nervous System, Nuclear Proteins, Phosphoglycerate Kinase, Stem Cells, Transcription Factors, Yolk Sac, Cell Hypoxia, Up-Regulation, Apoptosis, Gene Deletion, Teratocarcinoma, Mice, Knockout, Mice, Hypoxia-Inducible Factor 1, Hypoxia-Inducible Factor 1, alpha Subunit
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