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Identification of SULF2 as a novel transcriptional target of p53 by use of integrated genomic analyses
- Source :
- Cancer research. 69(4)
- Publication Year :
- 2009
-
Abstract
- Microarray analysis has been useful for identifying the targets of many transcription factors. However, gene expression changes in response to transcription factor perturbation reveal both direct transcriptional targets and secondary gene regulation. By integrating RNA interference, gene expression profiling, and chromatin immunoprecipitation technologies, we identified a set of 32 direct transcriptional targets of the tumor suppressor p53. Of these 32 genes, 11 are not currently associated with the core p53 pathway. From among these novel pathway members, we focused on understanding the connection between p53 and SULF2, which encodes an extracellular heparan sulfate 6-O-endosulfatase that modulates the binding of growth factors to their cognate receptors and that has been shown to function as a tumor suppressor. Genetic and pharmacologic perturbation of p53 directly influences SULF2 expression, and similar to silencing of TP53, RNA interference–mediated suppression of SULF2 results in an impaired senescence response of cells to genotoxic stress. Thus, our integrated genomic approach has led to the identification of a novel mediator of p53 network biology. [Cancer Res 2009;69(4):1368–74]
- Subjects :
- Cancer Research
Carcinoma, Hepatocellular
Tumor suppressor gene
Transcription, Genetic
Antineoplastic Agents
Bone Neoplasms
Biology
Polymerase Chain Reaction
RNA interference
Genes, Reporter
Cell Line, Tumor
Gene expression
Gene silencing
Humans
Transcription factor
DNA Primers
Oligonucleotide Array Sequence Analysis
Genetics
Regulation of gene expression
Genomic Library
Osteosarcoma
Genome, Human
Liver Neoplasms
Gene Amplification
Cell biology
Gene expression profiling
Oncology
Gene Expression Regulation
Sulfatases
Sulfotransferases
Tumor Suppressor Protein p53
Chromatin immunoprecipitation
Transcription Factors
Subjects
Details
- ISSN :
- 15387445
- Volume :
- 69
- Issue :
- 4
- Database :
- OpenAIRE
- Journal :
- Cancer research
- Accession number :
- edsair.doi.dedup.....9a933cf9fa92d387813bb516e6eb28c2