| First Author | Kwon CH | Year | 2008 |
| Journal | Cancer Res | Volume | 68 |
| Issue | 9 | Pages | 3286-94 |
| PubMed ID | 18451155 | Mgi Jnum | J:134611 |
| Mgi Id | MGI:3789409 | Doi | 10.1158/0008-5472.CAN-07-6867 |
| Citation | Kwon CH, et al. (2008) Pten haploinsufficiency accelerates formation of high-grade astrocytomas. Cancer Res 68(9):3286-94 |
| abstractText | 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. |
