TY - JOUR
T1 - Identification and classification of p53-regulated genes
AU - Yu, Jian
AU - Zhang, Lin
AU - Hwang, Paul M.
AU - Rago, Carlo
AU - Kinzler, Kenneth W.
AU - Vogelstein, Bert
PY - 1999/12/7
Y1 - 1999/12/7
N2 - Sequence-specific transactivation by p53 is essential to its role as a tumor suppressor. A modified tetracycline-inducible system was established to search for transcripts that were activated soon after p53 induction. Among 9,954 unique transcripts identified by serial analysis of gene expression, 34 were increased more than 10-fold; 31 of these had not previously been known to be regulated by p53. The transcription patterns of these genes, as well as previously described p53-regulated genes, were evaluated and classified in a panel of widely studied colorectal cancer cell lines. 'Class I' genes were uniformly induced by p53 in all cell lines; 'class II' genes were induced 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 their induction, their induction by clinically relevant chemotherapeutic agents, the absolute requirement for p53 in this induction, and their inducibility by p73, a p53 homolog. The results revealed substantial heterogeneity in the transcriptional responses to p53, even in cells derived from a single epithelial cell type, and pave the way to a deeper understanding of p53 tumor suppressor action.
AB - Sequence-specific transactivation by p53 is essential to its role as a tumor suppressor. A modified tetracycline-inducible system was established to search for transcripts that were activated soon after p53 induction. Among 9,954 unique transcripts identified by serial analysis of gene expression, 34 were increased more than 10-fold; 31 of these had not previously been known to be regulated by p53. The transcription patterns of these genes, as well as previously described p53-regulated genes, were evaluated and classified in a panel of widely studied colorectal cancer cell lines. 'Class I' genes were uniformly induced by p53 in all cell lines; 'class II' genes were induced 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 their induction, their induction by clinically relevant chemotherapeutic agents, the absolute requirement for p53 in this induction, and their inducibility by p73, a p53 homolog. The results revealed substantial heterogeneity in the transcriptional responses to p53, even in cells derived from a single epithelial cell type, and pave the way to a deeper understanding of p53 tumor suppressor action.
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U2 - 10.1073/pnas.96.25.14517
DO - 10.1073/pnas.96.25.14517
M3 - Article
C2 - 10588737
AN - SCOPUS:0033453226
VL - 96
SP - 14517
EP - 14522
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
SN - 0027-8424
IS - 25
ER -