Adenovirus-mediated transfer of the p53 gene produces rapid and generalized death of human glioma cells via apoptosis.
Wild-type p53 is involved in several aspects of cell cycle control and suppression of transformation, inducing either apoptosis or G1 block in cell cycle progression. Using a recombinant adenovirus containing the wild-type p53 cDNA, the biological effects of the newly expressed wild-type p53 protein were examined in six human glioma cell lines. Three cell lines (U-251 MG, U-373 MG, and A-172) expressed endogenous mutant p53, and the other three (U-87 MG, EFC-2, and D54 MG) expressed wild-type p53. The restoration of normal p53-encoded protein in the mutant cell lines induced apoptosis as assessed by morphological studies using nuclear staining, electron microscopy, and flow cytometric assays. In wild-type p53 cell lines, however, the overexpression of wild-type p53 did not result in apoptosis but inhibited cellular proliferation rather drastically and modified the neoplastic phenotype. Differential effects suggest two pathways for glioma oncogenesis and a possible therapeutic strategy.
Gomez-Manzano
C
C
Department of Neuro-Oncology, University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.
Fueyo
J
J
Kyritsis
A P
AP
Steck
P A
PA
Roth
J A
JA
McDonnell
T J
TJ
Steck
K D
KD
Levin
V A
VA
Yung
W K
WK
D000260:Adenoviruses, Human; D017209:Apoptosis; D015153:Blotting, Western; D002455:Cell Division; D002460:Cell Line; D005434:Flow Cytometry; D015870:Gene Expression; D016158:Genes, p53; D005822:Genetic Vectors; D005910:Glioma / Q000235:genetics; D006720:Homozygote; D006801:Humans; D007700:Kinetics; D011994:Recombinant Proteins / Q000096:biosynthesis; D013997:Time Factors; D014162:Transfection / Q000379:methods*; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis*
D011994:Recombinant Proteins; D016159:Tumor Suppressor Protein p53