Identifying genes regulated in a Myc-dependent manner.
The c-myc proto-oncogene can direct a diverse array of biological activities, including cell cycle progression, apoptosis, and differentiation. It is believed that Myc can affect this wide variety of activities by functioning as a regulator of gene transcription, although few targets have been identified to date. To delineate the molecular program regulated downstream of Myc, we used a cDNA microarray approach and identified 52 putative targets out of >6000 cDNAs analyzed. To further distinguish the subset of genes whose regulation was dependent upon Myc per se from those regulated in response to activation of general mitogenic or apoptotic programs, the putative cDNA targets were then screened by a series of assays. By this approach 37 putative targets were ruled out and 15 Myc target genes were uncovered. Interestingly, comparing our results with other high throughput screens reveals that certain putative Myc targets previously reported are shown not to be regulated downstream of Myc (e.g. ribosomal proteins, HSP90beta), whereas others are further supported by our analyses (e.g. pdgfbetar, nucleolin). The identity of genes specifically regulated downstream of Myc provides the critical tools required to understand the role Myc holds in the transformation process and to delineate how Myc functions as a regulator of gene transcription.
Watson
John D
JD
Ontario Cancer Institute and Department of Medical Biophysics, University of Toronto, Toronto, Ontario M5G 2M9, Canada.
Oster
Sara K
SK
Shago
Mary
M
Khosravi
Fereshteh
F
Penn
Linda Z
LZ
D000818:Animals; D017209:Apoptosis / Q000235:genetics; D015152:Blotting, Northern; D002453:Cell Cycle / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics; D002478:Cells, Cultured; D018076:DNA, Complementary / Q000235:genetics; D005347:Fibroblasts; D005786:Gene Expression Regulation; D016259:Genes, myc; D009687:Nuclear Proteins / Q000235:genetics; D000090243:Nucleophosmin; D020411:Oligonucleotide Array Sequence Analysis; D010750:Phosphoproteins / Q000235:genetics; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics; D011506:Proteins / Q000235:genetics; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics*; D016601:RNA-Binding Proteins / Q000235:genetics; D000097796:Nucleolin
D018076:DNA, Complementary; D009687:Nuclear Proteins; D000090243:Nucleophosmin; D010750:Phosphoproteins; D017395:Plasminogen Activator Inhibitor 1; D011506:Proteins; D016271:Proto-Oncogene Proteins c-myc; D016601:RNA-Binding Proteins; D000097796:Nucleolin