Up-regulation of the proapoptotic mediators Bax and Bak after adenovirus-mediated p53 gene transfer in lung cancer cells

Overexpression of wild-type p53 in cancer cells by adenovirus-mediated p53 gene transfer can result in the induction of apoptosis, To identify the pot ential mediators of this p53-induced apoptosis, we examined apoptotic prote in levels in human lung cancer cells after Adp53 gene transfer, We observed up-regulation of Bar and Bah protein levels 18-36 h after transduction wit h Adp53 in H1299, H358, and H322 lung cancer cells, Contrary to expected ob servations, no changes in Bcl-2 and Bcl-X-L protein levels were observed. M orphological cell changes and terminal deoxynucleotidyl transferase-mediate d dUTP-biotin nick end labeling staining showed evidence of apoptosis in al l cell lines 48 h after transduction with Adp53, These results indicate tha t the induction of apoptosis by adenovirus-mediated p53 transfer may be med iated by the induction of proapoptotic mechanisms rather than suppression o f antiapoptotic mechanisms.