Modeling mutations in the G(1) arrest pathway in human gliomas: overexpression of CDK4 but not loss of INK4a-ARF induces hyperploidy in cultured mouse astrocytes
Ec. Holland et al., Modeling mutations in the G(1) arrest pathway in human gliomas: overexpression of CDK4 but not loss of INK4a-ARF induces hyperploidy in cultured mouse astrocytes, GENE DEV, 12(23), 1998, pp. 3644-3649
Nearly all human gliomas exhibit alterations in one of three genetic loci g
overning G(1) arrest: INK4a-ARF, CDK4, or RE. 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 overexp
ressing 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 an
d convert to a tetraploid state at high efficiency; in contrast, INK4a-ARF-
deficient cells remain pseudodiploid, consistent with properties observed i
n human gliomas with corresponding lesions in these genes.