ETS-1 converts endothelial cells to the angiogenic phenotype by inducing the expression of matrix metalloproteinases and integrin beta3.
The transcription factor ETS-1 is induced in endothelial cells (ECs) by angiogenic growth factors and the specific elimination of ETS-1 synthesis by antisense oligodeoxynucleotide inhibited angiogenesis in vitro (Iwasaka et al., 1996, J Cell Physiol 169:522-531). To understand the precise role of ETS-1 in angiogenesis, we established both high and low ETS-1 expression EC lines and compared angiogenic properties of these cell lines with those of the parental murine EC line, MSS-31. Although growth rate was almost identical for each cell line, the invasiveness was markedly enhanced in high ETS-1 expression cells and reduced in low ETS-1 expression cells compared with that of parental cells. The gene expressions of matrix metalloproteinases (MMP-1, MMP-3, and MMP-9) and gelatinolytic activity of MMP-9 were significantly increased in high ETS-1 expression cells. Low ETS-1 expression cells could not spread on a vitronectin substratum, and the phosphorylation of focal adhesion kinase was markedly impaired because of the reduced expression of integrin beta3. These results indicate that ETS-1 is a principal regulator that converts ECs to the angiogenic phenotype.
Department of Vascular Biology, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan.
N
N
Oda
M
M
Abe
Y
Y
Sato
D000199:Actins / Q000096:biosynthesis; D000818:Animals; D015703:Antigens, CD / Q000235:genetics*; D001483:Base Sequence; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002455:Cell Division; D002460:Cell Line; D017364:Collagenases / Q000235:genetics; D017931:DNA Primers / Q000235:genetics; D004730:Endothelium, Vascular / Q000166:cytology* / Q000378:metabolism*; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D015870:Gene Expression; D039661:Integrin beta3; D016023:Integrins / Q000235:genetics; D020781:Matrix Metalloproteinase 1; D019278:Matrix Metalloproteinase 3 / Q000235:genetics; D020780:Matrix Metalloproteinase 9; D008666:Metalloendopeptidases / Q000235:genetics*; D051379:Mice; D018919:Neovascularization, Physiologic; D010641:Phenotype; D010980:Platelet Membrane Glycoproteins / Q000235:genetics*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D050784:Proto-Oncogene Protein c-ets-1; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D050783:Proto-Oncogene Proteins c-ets; D019030:Receptors, Vitronectin / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D016596:Vinculin / Q000378:metabolism
D000199:Actins; D015703:Antigens, CD; D015815:Cell Adhesion Molecules; D017931:DNA Primers; C494042:Ets1 protein, mouse; D039661:Integrin beta3; D016023:Integrins; D010980:Platelet Membrane Glycoproteins; D050784:Proto-Oncogene Protein c-ets-1; D011518:Proto-Oncogene Proteins; D050783:Proto-Oncogene Proteins c-ets; D019030:Receptors, Vitronectin; D014157:Transcription Factors; C064660:integrin alphaVbeta5; D016596:Vinculin; D011505:Protein-Tyrosine Kinases; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496051:Ptk2 protein, mouse; D017364:Collagenases; D008666:Metalloendopeptidases; D019278:Matrix Metalloproteinase 3; D020780:Matrix Metalloproteinase 9; D020781:Matrix Metalloproteinase 1