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Publication : Early inactivation of p53 tumor suppressor gene cooperating with NF1 loss induces malignant astrocytoma.

First Author  Zhu Y Year  2005
Journal  Cancer Cell Volume  8
Issue  2 Pages  119-30
PubMed ID  16098465 Mgi Jnum  J:101868
Mgi Id  MGI:3605594 Doi  10.1016/j.ccr.2005.07.004
Citation  Zhu Y, et al. (2005) Early inactivation of p53 tumor suppressor gene cooperating with NF1 loss induces malignant astrocytoma. Cancer Cell 8(2):119-30
abstractText  Malignant astrocytoma, the most prevalent primary brain tumor, is resistant to all known therapies and frequently harbors mutations that inactivate p53 and activate Ras signaling. We have generated mouse strains that lack p53 and harbor a conditional allele of the NF1 tumor suppressor that negatively regulates Ras signaling. The mice develop malignant astrocytomas with complete penetrance. The majority of tumors display characteristics of glioblastoma multiforme with concomitant alteration of signaling pathways previously described in the human counterparts of this neoplasm. We find that the sequence of tumor suppressor inactivation influences tumorigenicity and that earliest evidence of tumor formation localizes to regions of the brain that contain a multipotent stem cell population capable of in vivo differentiation into neurons and glia.
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