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 G(1) bloc k 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. T hree cell lines (U-251 MG, U-373 MG, and A-172) expressed endogenous m utant 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 mu tant cell lines induced apoptosis as assessed by morphological studies using nuclear staining, electron microscopy, and flow cytometric assa ys. In wild-type p53 cell lines, however, the overexpression of wild-t ype p53 did not result in apoptosis but inhibited cellular proliferati on rather drastically and modified the neoplastic phenotype. Different ial effects suggest two pathways for glioma oncogenesis and a possible therapeutic strategy.