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 responsible for apoptosis induced by etoposide, a p53 activating topoisomerase II inhibitor used clinically as an antitumor agent. 62 Individual mRNAs whose mass changed significantly were identified after screening oligonucleotide arrays capable of detecting 6591 unique human mRNA species. 12 (Nine induced and three repressed) of the etoposide-responsive genes were further studied 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 be the novel p53 target genes and the others appear to be p53-independent. Based upon these findings, the signalling pathways that possibly mediate etoposide-induced apoptosis are proposed.
Wang
Y
Y
Department of Molecular Biology, Parke-Davis Pharmaceutical Research, Division of Warner-Lambert Company, Ann Arbor, MI 48105, USA.
Rea
T
T
Bian
J
J
Gray
S
S
Sun
Y
Y
D017209:Apoptosis / Q000235:genetics*; D015152:Blotting, Northern; D005047:Etoposide / Q000494:pharmacology*; D015870:Gene Expression; D006801:Humans; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology*; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D019384:Nucleic Acid Synthesis Inhibitors; D016159:Tumor Suppressor Protein p53; D005047:Etoposide