%0 Journal Article
%T Identification and Regulation of c-Myb Target Genes in MCF-7 Cells
%A Anita M Quintana
%A Fan Liu
%A John P O'Rourke
%A Scott A Ness
%J BMC Cancer
%D 2011
%I BioMed Central
%R 10.1186/1471-2407-11-30
%X We used chromatin immunoprecipitation coupled with whole genome promoter tiling microarrays to identify endogenous c-Myb target genes in human MCF-7 breast cancer cells and characterized the activity of c-Myb at a panel of target genes during different stages of estrogen deprivation and stimulation.By using different antibodies and different growth conditions, the c-Myb protein was found associated with over 10,000 promoters in MCF-7 cells, including many genes that encode cell cycle regulators or transcription factors and more than 60 genes that encode microRNAs. Several previously identified c-Myb target genes were identified, including CCNB1, MYC and CXCR4 and novel targets such as JUN, KLF4, NANOG and SND1. By studying a panel of these targets to validate the results, we found that estradiol stimulation triggered the association of c-Myb with promoters and that association correlated with increased target gene expression. We studied one target gene, CXCR4, in detail, showing that c-Myb associated with the CXCR4 gene promoter and activated a CXCR4 reporter gene in transfection assays.Our results show that c-Myb associates with a surprisingly large number of promoters in human cells. The results also suggest that estradiol stimulation leads to large-scale, genome-wide changes in c-Myb activity and subsequent changes in gene expression in human breast cancer cells.The importance of the c-Myb transcription factor in breast cancer is closely linked to the response to estrogen [1]. Expression of the c-myb (MYB) gene is associated with expression of estrogen receptors (ERs) in breast tumors [2,3]. (Note: We use c-Myb and c-myb to distinguish between the protein and gene, respectively.) Regulation by ERs has been implicated in the post-transcriptional regulation of c-myb gene expression [4] and the c-myb gene is involved in recurrent translocations in some breast tumors that are positive for expression of ERs [5]. The c-myb gene is induced by activation of ERs in breast
%U http://www.biomedcentral.com/1471-2407/11/30