| First Author | Gutmann DH | Year | 1999 |
| Journal | Oncogene | Volume | 18 |
| Issue | 31 | Pages | 4450-9 |
| PubMed ID | 10442636 | Mgi Jnum | J:56902 |
| Mgi Id | MGI:1342880 | Doi | 10.1038/sj.onc.1202829 |
| Citation | Gutmann DH, et al. (1999) Haploinsufficiency for the neurofibromatosis 1 (NF1) tumor suppressor results in increased astrocyte proliferation. Oncogene 18(31):4450-9 |
| abstractText | Individuals affected with neurofibromatosis 1 (NF1) harbor increased numbers of GFAP-immunoreactive cerebral astrocytes and develop astrocytomas that can lead to blindness and death. Mice heterozygous for a targeted Nf1 mutation (Nf1+/-) were employed as a model for the human disease to evaluate the hypothesis that reduced NF1 protein (neurofibromin) expression may confer a growth advantage for astrocytes, such that inactivation of only one NF1 allele is sufficient for abnormal astrocyte proliferation. Here, we report that Nf17+/- mice have increased numbers of cerebral astrocytes and increased astrocyte proliferation compared to wild-type littermates. Intriguingly, primary Nf1+/- astrocyte cultures failed to demonstrate a cell-autonomous growth advantage unless they were cocultured with C17 neuronal cells. This C17 neuronal cell-induced Nf1+/- increase in proliferation was blocked by MEK inhibition (PD98059), suggesting a p21-ras-dependent effect. Furthermore, mice heterozygous for a targeted mutation in another GAP molecule, p120-GAP, demonstrated no increases in cerebral astrocyte number. These findings suggest that reduced NF1 expression results in a cell context-dependent increase in astrocyte proliferation that may be sufficient for the development of astrocytic growth abnormalities in patients with NF1. |
