Identification and classification of p53-regulated genes

Sequence-specific transactivation by p53 is essential to its role as a tumo r suppressor. A modified tetracycline-inducible system was established to s earch for transcripts that were activated soon after p53 induction. Among 9 ,954 unique transcripts identified by serial analysis of gene expression, 3 4 were increased more than 10-fold; 31 of these had not previously been kno wn to be regulated by p53. The transcription patterns of these genes, as we ll as previously described p53-regulated genes, were evaluated and classifi ed in a panel of widely studied colorectal cancer cell lines. "Class I" gen es were uniformly induced by p53 in all cell lines; "class II" genes were i nduced in a subset of the lines; and "class III" genes were not induced in any of the lines. These genes were also distinguished by the timing of thei r induction, their induction by clinically relevant chemotherapeutic agents , the absolute requirement for p53 in this induction, and their inducibilit y by p73, a p53 homolog. The results revealed substantial heterogeneity in the transcriptional responses to p53. even in cells derived from a single e pithelial cell type, and pave the way to a deeper understanding of p53 tumo r suppressor action.