Angiogenesis inhibition by transdominant mutant Ets-1

The expression of transcription factor Ets-1 is induced in endothelial cell s (ECs) by angiogenic factor; and in turn Ets-1 converts ECs to angiogenic invasive phenotype. In order to control angiogenesis, we constructed a tran sdominant 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 ade novirus 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 angiog enic inhibition. J. Cell. Physiol. 184:255-262, 2000. (C) 2000 Wiley-Liss, Inc.