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

Mice lacking the AML1/PEBP2 alpha B/CBFa2 gene or PEBP2 beta/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 ive examined whether PEBP2/CBF plays any role in angiogenesis besides that in definitive hematopoiesis, We found that AML1/ PEBP2 alpha B/CBFa2, PEBP2 alpha A/CBFa1, and PEBP2 beta/ CBFb were expressed in a murine endothelial cell Line MISS31, The expression of these molecules as cell 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 tells was confirmed at the site of angiogenesis in vivo, To further clarify the role of PEBP2/CF 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.