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HIF‐1α is required for solid tumor formation and embryonic vascularization
Author(s) -
Ryan Heather E.,
Lo Jessica,
Johnson Randall S.
Publication year - 1998
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/17.11.3005
Subject(s) - biology , embryonic stem cell , microbiology and biotechnology , solid tumor , cancer research , genetics , cancer , gene
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‐1α. To study the role of the transcriptional hypoxic response in vivo we have targeted the murine HIF‐1α gene. Loss of HIF‐1α 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‐1α 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‐1α in controlling both embryonic and tumorigenic responses to variations in microenvironmental oxygenation.