26
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: not found

      HIF-1 alpha is required for solid tumor formation and embryonic vascularization.

      1 , ,
      The EMBO journal
      Oxford University Press (OUP)

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          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.

          Related collections

          Author and article information

          Journal
          EMBO J
          The EMBO journal
          Oxford University Press (OUP)
          0261-4189
          0261-4189
          Jun 01 1998
          : 17
          : 11
          Affiliations
          [1 ] Department of Biology, University of California, San Diego, La Jolla, CA 92093-0366, USA.
          Article
          10.1093/emboj/17.11.3005
          1170640
          9606183
          8ec2c250-82cf-4457-98e5-69234efee931
          History

          Comments

          Comment on this article