References
Query Results -- Details
MGI Accession ID: MGI:3789409
J Number: J:134611
Other Accession IDs:
Title: Pten haploinsufficiency accelerates formation of high-grade astrocytomas.
Authors: Kwon CH; Zhao D; Chen J; Alcantara S; Li Y; Burns DK; Mason RP; Lee EY; Wu H; Parada LF
Journal: Cancer Res
Volume: 68
Issue: 9
Date: 2008 May 1
Year: 2008
Pages: 3286-94
Review Status: Peer Reviewed
Abstract:
We previously reported that central nervous system (CNS) inactivation of Nf1 and p53 tumor suppressor genes in mice results in the development of low-grade to high-grade progressive astrocytomas. When the tumors achieve high grade, they are frequently accompanied by Akt activation, reminiscent of the frequent association of PTEN mutations in human high-grade glioma. In the present study, we introduced CNS heterozygosity of Pten into the Nf1/p53 astrocytoma model. Resulting mice had accelerated morbidity, shortened survival, and full penetrance of high-grade astrocytomas. Haploinsufficiency of Pten accelerated formation of grade 3 astrocytomas, whereas loss of Pten heterozygosity and Akt activation coincided with progression into grade 4 tumors. These data suggest that successive loss of each Pten allele may contribute to de novo formation of high-grade astrocytoma and progression into glioblastoma, respectively, thus providing insight into the etiology of primary glioblastoma. The presence of ectopically migrating neural stem/progenitor lineage cells in presymptomatic Pten-deficient mutant brains supports the notion that these tumors may arise from stem/progenitor cells.
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