Identification of the genes responsive to etoposide-induced apoptosis: application of DNA chip technology

DNA chip technology was used in an attempt to identify target genes respons ible for apoptosis induced by etoposide, a p53 activating topoisomerase IT inhibitor used clinically as an antitumor agent. 62 Individual mRNAs whose mass changed significantly mere identified after screening oligonucleotide arrays capable of detecting 6591 unique human mRNA species. 12 (Nine induce d and three repressed) of the etoposide-responsive genes were further studi ed by Northern analysis and an agreement rate of 92% was reached. Among the 12 genes studied, two (WAF1/p21 and PCNA) are known p53 regulatory genes, two (glutathione peroxidase and S100A2 calcium-binding protein) appear to b e the novel p53 target genes and the others appear to be p53-independent. B ased upon these findings, the signalling pathways that possibly mediate eto poside-induced apoptosis are proposed. (C) 1999 Federation of European Bioc hemical Societies.