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Development and malignant progression of astrocytomas in GFAP-v-src transgenic mice
- Source :
- Scopus-Elsevier
- Publication Year :
- 1997
-
Abstract
- 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.
- Subjects :
- Male
Vascular Endothelial Growth Factor A
Cancer Research
Genes, Viral
Endothelial Growth Factors
Malignant transformation
Central Nervous System Neoplasms
Mice
chemistry.chemical_compound
Tumor Cells, Cultured
1306 Cancer Research
Gliosis
Transgenes
Lymphokines
Mice, Inbred C3H
Mice, Inbred ICR
Glial fibrillary acidic protein
biology
Vascular Endothelial Growth Factors
Astrocytoma
Cell Hypoxia
Neoplasm Proteins
Astrogliosis
Gene Expression Regulation, Neoplastic
Vascular endothelial growth factor
Genes, src
Vascular endothelial growth factor A
Disease Progression
Female
medicine.symptom
Gene Expression Regulation, Viral
Recombinant Fusion Proteins
10208 Institute of Neuropathology
Mice, Nude
Mice, Transgenic
610 Medicine & health
Oncogene Protein pp60(v-src)
1311 Genetics
Glioma
Glial Fibrillary Acidic Protein
Genetics
medicine
1312 Molecular Biology
Animals
Receptors, Growth Factor
Molecular Biology
Receptor Protein-Tyrosine Kinases
medicine.disease
Mice, Inbred C57BL
Receptors, Vascular Endothelial Growth Factor
chemistry
Immunology
biology.protein
Cancer research
570 Life sciences
Glioblastoma
Neoplasm Transplantation
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Scopus-Elsevier
- Accession number :
- edsair.doi.dedup.....a1ba5073a9c2a92122b9947086c6a20e