Angiogenesis inhibition by transdominant mutant Ets-1.
The expression of transcription factor Ets-1 is induced in endothelial cells (ECs) by angiogenic factor; and in turn Ets-1 converts ECs to angiogenic invasive phenotype. In order to control angiogenesis, we constructed a transdominant mutant Ets-1 (TMEts-1) which acts as a dominant negative molecule. This molecule inhibited the DNA binding and the transactivation activity of the wild-type Ets-1. Stable transfection of murine endothelial cell line MSS31 cells with the TMets-1 gene impaired angiogenic activities including proliferation, migration, invasion, and tube formation in type-1 collagen gel. Finally, we incorporated the TMets-1 gene into a non-proliferative adenovirus vector, designated as AdTMets-1. AdTMets-1 significantly inhibited angiogenesis in the Matrigel plugs injected into the subcutaneous tissue of C57BL mice. These results indicate that TMets-1 would be a tool for angiogenic inhibition.
Nakano
T
T
Department of Vascular Biology, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan.
Abe
M
M
Tanaka
K
K
Shineha
R
R
Satomi
S
S
Sato
Y
Y
D016475:3T3 Cells; D000256:Adenoviridae / Q000235:genetics / Q000378:metabolism; D020533:Angiogenesis Inhibitors / Q000378:metabolism*; D000818:Animals; D004727:Endothelium / Q000378:metabolism; D005822:Genetic Vectors / Q000235:genetics / Q000378:metabolism; D051379:Mice; D009154:Mutation; D009389:Neovascularization, Pathologic / Q000378:metabolism; D050784:Proto-Oncogene Protein c-ets-1; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D050783:Proto-Oncogene Proteins c-ets; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014162:Transfection / Q000235:genetics; D014407:Tumor Cells, Cultured
D020533:Angiogenesis Inhibitors; C494042:Ets1 protein, mouse; D050784:Proto-Oncogene Protein c-ets-1; D011518:Proto-Oncogene Proteins; D050783:Proto-Oncogene Proteins c-ets; D014157:Transcription Factors