| Identification and classification
of p53-regulated genes
Jian Yu*,
Lin Zhang, Paul M. Hwang, Carlo Rago, Kenneth
W. Kinzler*, and Bert Vogelstein*,§
*Graduate
Program in Human Genetics and Molecular Biology, The Johns
Hopkins University, Baltimore, MD 21205; and The Johns
Hopkins Oncology Center, and The Howard Hughes Medical Institute,
The Johns Hopkins University School of Medicine, Baltimore,
MD 21231
PNAS Vol.
96, Issue 25, 14517-14522, December 7, 1999
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Abstract
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.
§ To whom reprint requests should
be addressed. E-mail: vogelbe@welch.jhu.edu.
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