NEU DIFFERENTIATION FACTOR (NDF), A DOMINANT ONCOGENE, CAUSES APOPTOSIS IN-VITRO AND IN-VIVO

Neu differentiation factor (NDF, also called neuregulin) is a potent i nducer of epithelial cell proliferation and has been shown to induce m ammary carcinomas in transgenic mice. Notwithstanding this proliferati ve effect, we have shown that a novel isoform of NDF can induce apopto sis when overexpressed. Here we report that this property also extends to other NDF isoforms and that the cytoplasmic portion of NDF is larg ely responsible for the apoptotic effect, whereas the proliferative ac tivity is likely to depend upon the secreted version of NDF. In accord ance with these contradictory properties, we find that tumors induced by NDF display extensive apoptosis in vivo. NDF is therefore an oncoge ne whose deregulation can induce transformation as well as apoptosis.