| First Author | Weissenberger J | Year | 1997 |
| Journal | Oncogene | Volume | 14 |
| Issue | 17 | Pages | 2005-13 |
| PubMed ID | 9160879 | Mgi Jnum | J:40335 |
| Mgi Id | MGI:87676 | Doi | 10.1038/sj.onc.1201168 |
| Citation | Weissenberger J, et al. (1997) Development and malignant progression of astrocytomas in GFAP-v-src transgenic mice. Oncogene 14(17):2005-13 |
| abstractText | We have generated a transgenic mouse model for astrocytoma by expressing the v-src kinase under control of the glial fibrillary acidic protein (GFAP) gene regulatory elements in astrocytes. Abnormal astrogliosis was observed in all transgenic animals already at 2 weeks postnatally, frequently followed by the development of dysplastic changes. Later, small proliferative foci arose, and overt astrocytoma developed in the brain and spinal cord in 14.4% of mice after a follow up time of 65 weeks. While early lesions were histologically consistent with low-grade astrocytoma, at later stages most tumors were highly mitotic and frankly malignant. Vascular endothelial growth factor (VEGF) was expressed by tumor cells already at early stages, suggesting induction by v-src, and it was most pronounced in pseudopalisading cells surrounding necrotic areas, implying additional upregulation by hypoxia. In larger lesions, mitotic activity and expression of flk-1, the cognate receptor of VEGF were induced in endothelial cells. Therefore, end-stage tumors mimicked the morphological and molecular characteristics of human glioblastoma multiforme. Time course and stochastic nature of the process indicate that v-src did not suffice for malignant transformation, and that astrocytomas were the result of a multistep process necessitating co-operation of additional genetic events. |
