Astrocyte inactivation of the pRb pathway predisposes mice to malignant astrocytoma development that is accelerated by PTEN mutation

Cancer Cell. 2002 Mar;1(2):157-68. doi: 10.1016/s1535-6108(02)00029-6.


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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aging
  • Animals
  • Apoptosis
  • Astrocytes / metabolism*
  • Astrocytes / pathology
  • Astrocytoma / genetics
  • Astrocytoma / metabolism*
  • Astrocytoma / pathology*
  • Brain / abnormalities
  • Brain / pathology
  • Cell Division
  • Enzyme Activation
  • Genetic Predisposition to Disease*
  • Heterozygote
  • Mice
  • Mice, Transgenic
  • Mutation / genetics
  • Organ Specificity
  • PTEN Phosphohydrolase
  • Phosphoric Monoester Hydrolases / genetics
  • Phosphoric Monoester Hydrolases / metabolism*
  • Protein Serine-Threonine Kinases*
  • Proto-Oncogene Proteins / metabolism
  • Proto-Oncogene Proteins c-akt
  • Retinoblastoma Protein / metabolism*
  • Signal Transduction*
  • Tumor Suppressor Protein p53 / metabolism
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / metabolism*


  • Proto-Oncogene Proteins
  • Retinoblastoma Protein
  • Tumor Suppressor Protein p53
  • Tumor Suppressor Proteins
  • Protein Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-akt
  • Phosphoric Monoester Hydrolases
  • PTEN Phosphohydrolase