Constitutive expression of the DNA-binding domain of Ets1 increases endothelial cell adhesion and stimulates their organization into capillary-like structures

• Published in: Oncogene Vol. 19; no. 6; pp. 762 - 772
• Main Authors: MATTOT, V, VERCAMER, C, SONCIN, F, CALMELS, T, HUGUET, C, FAFEUR, V, VANDENBUNDER, B
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing 10.02.2000; Nature Publishing Group; Nature Publishing Group [1987-....]
• Subjects: 3T3 Cells; Angiogenesis; Animals; Aorta; Biological and medical sciences; Blood vessels; Brain - blood supply; Cancer; Capillaries - cytology; Cell adhesion; Cell adhesion & migration; Cell Adhesion - genetics; Cell Division; Cell lines; Cell Movement; Cell proliferation; Cells, Cultured; Collagen; Coronary vessels; Cytology; Cytoskeleton; Cytoskeleton - ultrastructure; DNA binding proteins; DNA, Complementary - genetics; Drug Combinations; Embryos; Endothelial cells; Endothelium, Vascular - cytology; Endothelium, Vascular - metabolism; Epithelial cells; ETS protein; Ets-1 protein; Ets1 protein; Fibroblast growth factor 2; Fibroblast Growth Factor 2 - pharmacology; Fundamental and applied biological sciences. Psychology; Gene expression; Gene regulation; Genetic aspects; Intercellular Junctions - ultrastructure; Laminin; Life Sciences; Mice; Molecular and cellular biology; Molecular genetics; Morphogenesis - genetics; Mutants; Neovascularization, Physiologic - genetics; Organ Specificity; Physiological aspects; Proteoglycans; Proto-Oncogene Protein c-ets-1; Proto-Oncogene Proteins - biosynthesis; Proto-Oncogene Proteins - genetics; Proto-Oncogene Proteins - physiology; Proto-Oncogene Proteins c-ets; Recombinant Fusion Proteins - physiology; Transcription factors; Transcription Factors - biosynthesis; Transcription Factors - genetics; Transcription Factors - physiology; Transcription. Transcription factor. Splicing. Rna processing; France; Angiogenesis; Vertebrata; Endothelial cell; Mammalia; Cell function; Cell line; Gene; Mouse; Rodentia; Mutation; Gene expression; Adhesion
• ISSN: 0950-9232; 1476-5594
• DOI: 10.1038/sj.onc.1203248

We previously reported that the Ets1 transcription factor is expressed in endothelial cells during angiogenesis both in normal and pathological development. We analyse here the effects of the stable expression of an Ets transdominant negative mutant (Ets1-DB), consisting in an Ets1 protein lacking its transactivation domain. A retrovirus containing the Ets1-DB sequence fused to an IRES-Neo sequence was designed and used to infect brain capillary (IBE) and aorta (MAE) mouse endothelial cell lines. Cells expressing this Ets1 mutant were examined for proliferation, migration and adhesion. Consistent changes were observed on cell morphology, with increased spreading and modifications in the organization of the cytoskeleton, and increased cell adhesion. We investigated the ability of endothelial cells to organise into capillary-like structures using three-dimensional gels. On Matrigel, all endothelial cell lines formed a cord-like network within 24 h, with an increased ability of Ets1-DB cells to spread on this substrate. In long term cultures, IBE cells expressing Ets1-DB showed a higher capacity to form branched structures; this effect was potentiated by FGF2. These results demonstrate a role of the Ets transcription factors in the regulation of the adhesive and morphogenetic properties of endothelial cells.