First Author | Xiao A | Year | 2002 |
Journal | Cancer Cell | Volume | 1 |
Issue | 2 | Pages | 157-68 |
PubMed ID | 12086874 | Mgi Jnum | J:77132 |
Mgi Id | MGI:2181090 | Doi | 10.1016/s1535-6108(02)00029-6 |
Citation | Xiao A, et al. (2002) Astrocyte inactivation of the pRb pathway predisposes mice to malignant astrocytoma development that is accelerated by PTEN mutation. Cancer Cell 1(2):157-68 |
abstractText | We have inactivated pRb, p107, and p130 in astrocytes by transgenic expression of T(121) (a truncated SV40 T antigen) under the GFAP promoter. Founder mice died perinatally with extensive expansion of neural precursor and anaplastic astrocyte populations. In astrocytes, aberrant proliferation and extensive apoptosis were induced. Using a conditional allele of T(121), early lethality was circumvented, and adult mice developed high-grade astrocytoma, in which regions of decreased apoptosis expressed activated Akt. Indeed, astrocytoma development was accelerated in a PTEN(+/-), but not p53(+/-), background. These studies establish a highly penetrant preclinical model for astrocytoma based on events observed in the human disease and further provide insight into the role of PTEN mutation in astrocytoma progression. |