[PDF][PDF] Astrocyte inactivation of the pRb pathway predisposes mice to malignant astrocytoma development that is accelerated by PTEN mutation
A Xiao, H Wu, PP Pandolfi, DN Louis, T Van Dyke - Cancer cell, 2002 - cell.com
A Xiao, H Wu, PP Pandolfi, DN Louis, T Van Dyke
Cancer cell, 2002•cell.comWe 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 …
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 …
Abstract
We have inactivated pRb, p107, and p130 in astrocytes by transgenic expression of T121 (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 T121, 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.
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