The N-myc oncogene in human neuroblastoma cells: Down-regulation of an angiogenesis inhibitor identified as activin A

Angiogenesis, the formation of new blood vessels, is seen during embryonic development and tumor progression, but the mechanisms have remained unclear . Recent data indicate that developmental and tumor angiogenesis can be ind uced by cellular oncogenes, leading to the enhanced activity of molecules s timulating angiogenesis. However, activated oncogenes might also facilitate angiogenesis by down-regulating endogenous inhibitors of angiogenesis. We report here that enhanced expression of the N-myc oncogene in human neurobl astoma cells down-regulates an inhibitor of endothelial cell proliferation, identified by amino acid sequencing as being identical with activin A, a d evelopmentally regulated protein. Down-regulation appears to involve intera ction of the N-Myc protein with the activin A promoter, In addition, activi n A inhibits both endothelial cell proliferation in vitro and angiogenesis in vivo, and it induces hemorrhage in vivo. We suggest that the N-myc-induc ed downregulation of activin A could contribute to developmental and tumor angiogenesis.