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Malignant Astrocytomas Originate from Neural Stem/Progenitor Cells in a Somatic Tumor Suppressor Mouse Model
Cancer Cell, Issue: 1, Volume: 15, Pages: 45-56. | 2009-01-01
0 Patent citations    270 Scholarly citations     Reference Count: 45
Sheila R Alcantara Llaguno;Jian Chen;Chang-Hyuk Kwon;Erica L Jackson;Yanjiao Li;Dennis K Burns;Arturo Alvarez-Buylla;Luis F Parada

摘要

Summary 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.


机构

University of Texas Southwestern Medical Center;Department of Developmental Biology, The University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390, USA.University of Texas Southwestern Medical CenterUniversity of Texas Southwestern Medical CenterUniversity of California, San FranciscoUniversity of Texas Southwestern Medical CenterUniversity of Texas Southwestern Medical CenterUniversity of California, San FranciscoUniversity of Texas Southwestern Medical Center


文献类型:

journal article;research support, n.i.h., extramural;research support, u.s. gov't, non-p.h.s.;research support, non-u.s. gov't;

出版商:

Cell Press

发表时间:

2009-01-01

基金信息

NINDS NIH HHS(5P50 NS052606)United States