Adenovirus-mediated Wild-type p53 Gene Transfer and Overexpression Induces Apoptosis of Human Glioma Cells Independent of Endogenous p53 Status

Mutation or inactivation of the p53 tumor suppression gene is an early alteration in the transformation of glial cells to gliomas. To study the effect of exogenous wild-type p53 on glioma cell growth, human glioma lines U251 MG, U87 MG and A172 were infected with an adenovirus vector expressing either wild-type p53 or bacterial lacZ. Rapid cell death occurred only in the p53-transduced cell lines and was characterized by nuclear condensation, formation of nucleosomal DNA ladders, and positive in situ end-labeling of DNA, suggesting that apoptosis had been induced. The U87 MG cell line that contains wild-type p53 as evidenced by wild-type p53-dependent transcription activity also underwent apoptosis within 2 to 3 days after infection. These results suggest that the presence of endogenous wild-type p53 does not preclude apoptosis by overexpression of exogenous p53.