Angiogenesis inhibition by transdominant mutant Ets-1

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Abstract
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. J. Cell. Physiol. 184:255–262, 2000.