title: Functional expression of human p21(WAF1/CIP1) gene in rat glioma cells suppresses tumor growth in vivo and induces radiosensitivity.
abstract: 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).
authors.affiliation: Department of Neurosurgery, Stanford University Medical Center, California 94305, USA.
authors.forename: M
authors.initials: M
authors.lastname: Hsiao
authors.forename: V
authors.initials: V
authors.lastname: Tse
authors.forename: J
authors.initials: J
authors.lastname: Carmel
authors.forename: E
authors.initials: E
authors.lastname: Costanzi
authors.forename: B
authors.initials: B
authors.lastname: Strauss
authors.forename: M
authors.initials: M
authors.lastname: Haas
authors.forename: G D
authors.initials: GD
authors.lastname: Silverberg
mesh_terms: D000818:Animals; D002455:Cell Division; D002470:Cell Survival; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000235:genetics* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000378:metabolism*; D016147:Genes, Tumor Suppressor; D005909:Glioblastoma / Q000378:metabolism*; D006801:Humans; D011836:Radiation Tolerance; D051381:Rats; D014407:Tumor Cells, Cultured
chemical_list: C493956:CDKN1A protein, human; C493958:Cdkn1a protein, rat; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D004791:Enzyme Inhibitors