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Publication : Malignant astrocytomas originate from neural stem/progenitor cells in a somatic tumor suppressor mouse model.

First Author  Alcantara Llaguno S Year  2009
Journal  Cancer Cell Volume  15
Issue  1 Pages  45-56
PubMed ID  19111880 Mgi Jnum  J:143505
Mgi Id  MGI:3827048 Doi  10.1016/j.ccr.2008.12.006
Citation  Alcantara Llaguno S, et al. (2009) Malignant astrocytomas originate from neural stem/progenitor cells in a somatic tumor suppressor mouse model. Cancer Cell 15(1):45-56
abstractText  Malignant astrocytomas are infiltrative and incurable brain tumors. Despite profound therapeutic implications, the identity of the cell (or cells) of origin has not been rigorously determined. We previously reported mouse models based on conditional inactivation of the human astrocytoma-relevant tumor suppressors p53, Nf1, and Pten, wherein through somatic loss of heterozygosity, mutant mice develop tumors with 100% penetrance. In the present study, we show that tumor suppressor inactivation in neural stem/progenitor cells is both necessary and sufficient to induce astrocytoma formation. We demonstrate in vivo that transformed cells and their progeny undergo infiltration and multilineage differentiation during tumorigenesis. Tumor suppressor heterozygous neural stem/progenitor cultures from presymptomatic mice show aberrant growth advantage and altered differentiation, thus identifying a pretumorigenic cell population.
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