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Neu differentiation factor (NDF), a dominant oncogene, causes apoptosis in vitro and in vivo
S Grimm1, E J Weinstein, I M Krane
1Department of Genetics, Harvard Medical School, and the Howard Hughes Medical Institute, Boston, Massachusetts 02115, USA.
Abstract:
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.
Insights
Neu differentiation factor (NDF) can trigger both cell growth and cell death. This oncogene
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- Neu differentiation factor (NDF), also known as neuregulin, is recognized for inducing epithelial cell proliferation.
- NDF has been implicated in the development of mammary carcinomas in transgenic mouse models.
Purpose of the Study:
- To investigate the dual role of NDF isoforms in cell proliferation and apoptosis.
- To determine the specific domains of NDF responsible for its proliferative and apoptotic activities.
- To examine the in vivo effects of NDF on tumor development, including apoptosis.
Main Methods:
- Overexpression of novel and known NDF isoforms in cellular models.
- Analysis of NDF's cytoplasmic and secreted portions to delineate functional domains.
- In vivo studies of NDF-induced tumors to assess apoptosis.
Main Results:
- NDF overexpression can induce apoptosis, a novel finding contrasting its known proliferative effects.
- The cytoplasmic portion of NDF is primarily responsible for inducing apoptosis.
- The secreted portion of NDF is linked to its proliferative activity.
- NDF-induced tumors in vivo exhibit significant levels of apoptosis.
Conclusions:
- NDF acts as a dual-acting oncogene, capable of inducing both cell transformation and apoptosis.
- Deregulation of NDF can lead to complex outcomes in tumorigenesis, involving both proliferation and cell death.
- Understanding the differential roles of NDF domains is crucial for its therapeutic targeting.