Mining for regulatory programs in the cancer transcriptome.
DNA microarrays have been widely applied to cancer transcriptome analysis. The Oncomine database contains a large collection of such data, as well as hundreds of derived gene-expression signatures. We studied the regulatory mechanisms responsible for gene deregulation in these cancer signatures by searching for the coordinate regulation of genes with common transcription factor binding sites. We found that genes with binding sites for the archetypal cancer transcription factor, E2F, were disproportionately overexpressed in a wide variety of cancers, whereas genes with binding sites for other transcription factors, such as Myc-Max, c-Rel and ATF, were disproportionately overexpressed in specific cancer types. These results suggest that alterations in pathways activating these transcription factors may be responsible for the observed gene deregulation and cancer pathogenesis.
Rhodes
Daniel R
DR
Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA.
Kalyana-Sundaram
Shanker
S
Mahavisno
Vasudeva
V
Barrette
Terrence R
TR
Ghosh
Debashis
D
Chinnaiyan
Arul M
AM
D001665:Binding Sites; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D019992:Databases as Topic; D050684:E2F Transcription Factors; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009369:Neoplasms / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D012045:Regulatory Sequences, Nucleic Acid; D015398:Signal Transduction; D013223:Statistics as Topic; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D014157:Transcription Factors