Abstract
In astrocytic neoplasms, the number of cells expressing glial fibrillary acidic protein (GFAP) is inversely proportional to the extent of anaplasia. The loss of GFAP expression, the principal marker of astroglial cells, in these tumors has been proposed to constitute a step in their development and progression. To test this hypothesis, we crossed p53-negative (p53−/−) mice, which frequently develop astrocytomas after intrauterine exposure to ethylnitrosourea, with GFAP-negative (GFAP−/−) mice or GFAP+/+ controls. Brain tumors of glial origin were found in 12 of 35 GFAP+/+ p53−/− mice (34%) and in 11 of 27 GFAP−/− p53−/− mice (41%). The two groups did not differ in the age at which tumors were detected or in tumor histology or progression. Thus, the loss of GFAP expression frequently seen in high-grade astrocytomas does not constitute a step in tumor development. Rather, it may represent the undifferentiated state of these cells.
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Acknowledgements
This article is dedicated to the memory of Professor Jan Pontén. We thank Dr Ricardo Feinstein (State Veterinary Institute, Uppsala, Sweden) for help with characterization of the tumors, Professor Christer Betsholtz for valuable discussions, and Dr Marcela Pekna for critical reading of the manuscript. This study was supported by grants from the Swedish Cancer Foundation (project no. 3622), the Swedish Medical Research Council (project no. 11548), the Swedish Society for Medicine, the Swedish Society for Medical Research, the King Gustaf V Foundation, Volvo Assar Gabrielsson Fond, and the Swedish Stroke Foundation.
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Wilhelmsson, U., Eliasson, C., Bjerkvig, R. et al. Loss of GFAP expression in high-grade astrocytomas does not contribute to tumor development or progression. Oncogene 22, 3407–3411 (2003). https://doi.org/10.1038/sj.onc.1206372
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DOI: https://doi.org/10.1038/sj.onc.1206372
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