Development and malignant progression of astrocytomas in GFAP-v-src transgenic mice (original) (raw)

Oncogene volume 14, pages 2005–2013 (1997)Cite this article

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.

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Authors and Affiliations

  1. Institute of Neuropathology, Dept. of Pathology, University Hospital of Zürich, Schmeizbergstrasse 12, Zürich, CH-8091, Switzerland
    Jakob Weissenberger, Joachim P Steinbach, Gerhard Malin, Salvatore Spada & Adriano Aguzzi
  2. Central Biological Laboratory, University Hospital of Zürich, Zürich, CH-8091, Switzerland
    Thomas Rülicke

Authors

  1. Jakob Weissenberger
  2. Joachim P Steinbach
  3. Gerhard Malin
  4. Salvatore Spada
  5. Thomas Rülicke
  6. Adriano Aguzzi

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Weissenberger, J., Steinbach, J., Malin, G. et al. Development and malignant progression of astrocytomas in GFAP-v-src transgenic mice.Oncogene 14, 2005–2013 (1997). https://doi.org/10.1038/sj.onc.1201168

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