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© The Rockefeller University Press, 0022-1007/1998/10/1535/ $5.00
The Journal of Experimental Medicine, Volume 188, Number 8, October 19, 1998 1535-1539

Brief Definitive Reports

Neu Differentiation Factor (NDF), a Dominant Oncogene, Causes Apoptosis In Vitro and In Vivo

Stefan Grimm, Edward J. Weinstein, Ian M. Krane, and Philip Leder

From the Department of Genetics, Harvard Medical School, and the Howard Hughes Medical Institute, Boston, Massachusetts 02115

Neu differentiation factor (NDF, also called neuregulin) is a potent inducer of epithelial cell proliferation and has been shown to induce mammary carcinomas in transgenic mice. Notwithstanding this proliferative effect, we have shown that a novel isoform of NDF can induce apoptosis when overexpressed. Here we report that this property also extends to other NDF isoforms and that the cytoplasmic portion of NDF is largely responsible for the apoptotic effect, whereas the proliferative activity is likely to depend upon the secreted version of NDF. In accordance with these contradictory properties, we find that tumors induced by NDF display extensive apoptosis in vivo. NDF is therefore an oncogene whose deregulation can induce transformation as well as apoptosis.

Key Words: Neu differentiation factor • neuregulin • apoptosis • tumors • TUNEL assay

Address correspondence to Philip Leder, Department of Genetics, Harvard Medical School and Howard Hughes Medical Institute, 200 Longwood Ave., Boston, MA 02115. Phone: 617-432-7662; Fax: 617-432-7944; E-mail: leder{at}rascal.med.harvard.edu

S. Grimm was supported by the AIDS Stipendium of the Deutsche Krebsforschungszentrum, Heidelberg, Germany, and by a grant from the Howard Hughes Medical Institute.

Stefan Grimm's present address is Max-Planck Institute for Biochemistry, Martinsried, Germany.

Ian M. Krane's present address is Genzyme Transgenics Inc., Framingham, MA.


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