Functional expression of human p21(WAF1/CIP1) gene in rat glioma cells suppresses tumor growth in vivo and induces radiosensitivity

Biochem Biophys Res Commun. 1997 Apr 17;233(2):329-35. doi: 10.1006/bbrc.1997.6450.


This study reports the successful growth suppression of a rat glioblastoma model (RT-2) both in vitro and in vivo by the insertion of p21(WAF1/CIP1), a negative cell cycle regulatory gene, into the tumor cells. Greater than 95% of the tumor cells expressed p21 protein after being infected with pCL based p21 retrovirus at 4x M.O.I. (multiplicity of infection). The p21-infected cells showed a 91% reduction in colony forming efficiency and a 66% reduction in growth rate. More prominent p21 staining was found in cells exhibiting histologic evidence of senescence. Intracranial implantation of the infected cells showed complete disappearance of the p21-infected cells at day 10 and long-term survival of the animals compared to controls. Injection of pCLp21 virus into tumor established in situ showed tumor necrosis and gene expression. In a clonogenic radiation survival assay, a 93% reduction of surviving colonies of p21-infected cells was seen in comparison to vector-infected control cells and to p53-infected cells after exposure to 8 Gy (800 rads).

Publication types

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

MeSH terms

  • Animals
  • Cell Division
  • Cell Survival
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins / genetics*
  • Cyclins / metabolism
  • Enzyme Inhibitors / metabolism*
  • Genes, Tumor Suppressor
  • Glioblastoma / metabolism*
  • Humans
  • Radiation Tolerance
  • Rats
  • Tumor Cells, Cultured


  • CDKN1A protein, human
  • Cdkn1a protein, rat
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins
  • Enzyme Inhibitors