Modeling mutations in the G1 arrest pathway in human gliomas: overexpression of CDK4 but not loss of INK4a-ARF induces hyperploidy in cultured mouse astrocytes. Academic Article uri icon

Overview

abstract

  • Nearly all human gliomas exhibit alterations in one of three genetic loci governing G1 arrest: INK4a-ARF, CDK4, or RB. To discern the roles of CDK4 amplification and INK4a-ARF loss in gliomagenesis, we compared the behavior of astrocytes lacking a functional INK4a-ARF locus with astrocytes overexpressing CDK4. Either a deficiency of p16(INK4a) and p19(ARF) or an increase in Cdk4 allows cultured astrocytes to grow without senescence. Astrocytes overexpressing CDK4 grow more slowly than INK4a-ARF-deficient astrocytes and convert to a tetraploid state at high efficiency; in contrast, INK4a-ARF-deficient cells remain pseudodiploid, consistent with properties observed in human gliomas with corresponding lesions in these genes.

publication date

  • December 1, 1998

Research

keywords

  • Astrocytes
  • Cyclin-Dependent Kinases
  • G1 Phase
  • Glioma
  • Proteins
  • Proto-Oncogene Proteins

Identity

PubMed Central ID

  • PMC317261

Scopus Document Identifier

  • 0032217155

Digital Object Identifier (DOI)

  • 10.1101/gad.12.23.3644

PubMed ID

  • 9851971

Additional Document Info

volume

  • 12

issue

  • 23