Overexpression of p21WAF1/CIP1 induces cell differentiation and growth inhibition in a human glioma cell line

Int J Cancer. 1998 Feb 9;75(4):643-8. doi: 10.1002/(sici)1097-0215(19980209)75:4<643::aid-ijc24>3.0.co;2-8.


p21WAF1/CIP1 is a downstream mediator of p53 and mediates growth arrest by inhibiting the action of G1 cyclin-dependent kinases. Since cellular differentiation is frequently characterized by G1 arrest, we examined whether p21WAF1/CIP1 overexpression would induce growth suppression and differentiation in p53-defective human glioma cells. Overexpression of p21WAF1/CIP1 resulted in an accumulation of cells in G1, altered morphology, growth arrest and cell differentiation. The extent of cell differentiation correlated with the level of p21WAF1/CIP1 as well as of proliferating cell nuclear antigen, cyclin E, and cdk 2, which associates with p21WAF1/CIP1. Our data suggest that gene transfer of p21WAF1/CIP1 may arrest glioma cell growth in vivo by committing malignant glioma cells to a pathway of terminal differentiation.

MeSH terms

  • CDC2-CDC28 Kinases*
  • Cell Cycle
  • Cell Differentiation
  • Colony-Forming Units Assay
  • Cyclin E / metabolism
  • Cyclin-Dependent Kinase 2
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclin-Dependent Kinases / metabolism
  • Cyclins / physiology*
  • Glial Fibrillary Acidic Protein / metabolism
  • Glioma / pathology
  • Glioma / physiopathology*
  • Humans
  • Proliferating Cell Nuclear Antigen / metabolism
  • Protein-Serine-Threonine Kinases / metabolism
  • Transfection
  • Tumor Cells, Cultured


  • CDKN1A protein, human
  • Cyclin E
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins
  • Glial Fibrillary Acidic Protein
  • Proliferating Cell Nuclear Antigen
  • Protein-Serine-Threonine Kinases
  • CDC2-CDC28 Kinases
  • CDK2 protein, human
  • Cyclin-Dependent Kinase 2
  • Cyclin-Dependent Kinases