Indispensable role of the transcription factor PEBP2/CBF in angiogenic activity of a murine endothelial cell MSS31

Oncogene. 2000 Jan 6;19(1):106-14. doi: 10.1038/sj.onc.1203257.

Abstract

Mice lacking the AML1/PEBP2alphaB/CBFa2 gene or PEBP2beta/CBFb gene exhibit a defect in definitive hematopoiesis and die in utero because of hemorrhage in the central nervous system. Hematopoiesis in the embryo is considered to be tightly associated with vascular development. Here we examined whether PEBP2/CBF plays any role in angiogenesis besides that in definitive hematopoiesis. We found that AML1/PEBP2alphaB/CBFa2, PEBP2alphaA/CBFa1, and PEBP2beta/CBFb were expressed in a murine endothelial cell line MSS31. The expression of these molecules as well as the DNA binding activity of PEBP2/CBF were augmented by angiogenic growth factors such as bFGF and VEGF. Moreover, the expression of PEBP2 alpha/CBFa protein in endothelial cells was confirmed at the site of angiogenesis in vivo. To further clarify the role of PEBP2/CBF in angiogenesis, we established permanent transfectants of PEBP2 beta-MYH11 gene, one that interacts with the runt domain of the alpha subunit and deregulates PEBP2/CBF in a dominant interfering manner. Proliferation, migration, and tube formation of the PEBP2 beta-MYH11 transfectants were significantly reduced in comparison with those activities of the mock transfectants. These results suggest that transcription factor PEBP2/CBF plays an important role in angiogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Core Binding Factor alpha Subunits
  • Core Binding Factor beta Subunit
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / physiology*
  • Endothelial Growth Factors / pharmacology
  • Endothelium, Vascular / physiology*
  • Fibroblast Growth Factor 2 / pharmacology
  • Lymphokines / pharmacology
  • Male
  • Mice
  • Neovascularization, Physiologic*
  • RNA, Messenger / analysis
  • Transcription Factor AP-2
  • Transcription Factors / genetics
  • Transcription Factors / physiology*
  • Transfection
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors

Substances

  • Cbfb protein, mouse
  • Core Binding Factor alpha Subunits
  • Core Binding Factor beta Subunit
  • DNA-Binding Proteins
  • Endothelial Growth Factors
  • Lymphokines
  • RNA, Messenger
  • Transcription Factor AP-2
  • Transcription Factors
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors
  • Fibroblast Growth Factor 2