Alterations in the gene expression profile of MCF-7 breast tumor cells in response to c-Jun.
MCF7 breast tumor cells overexpressing human c-Jun exhibit a transformed phenotype characterized not only by increased tumorigenicity but also by enhanced motility and invasion. The cellular phenotypic response to c-Jun overexpression is likely due, at least in part, to altered patterns of gene expression. In order to begin to understand the complexities by which elevated production of c-Jun alters the state of the cell, we have profiled the expression of 588 different genes by comparative hybridization. By using this approach, we have identified a total of 21 upregulated or downregulated gene targets responsive to c-Jun overexpression. Interestingly, 8 of these genes have been previously found associated with c-Jun or AP-1 activity and therefore provide internal validation for this approach to target gene discovery. The remaining 13 genes represent potential new c-Jun regulated target genes. Genomic sequence information was available for 15 of the 21 genes identified in this screen. Analysis of these genomic sequences revealed the presence of AP-1 or AP-1-like sequences in 12 of the 15 genes examined. Consistent with a direct mechanism of target regulation by c-Jun, gel shift analysis of selected AP-1-containing promoter regions revealed elevated and specific binding by proteins present in nuclear extracts of c-Jun expressing MCF7 cells.
Rinehart-Kim
J
J
Department of Microbiology and Molecular Cell Biology, Eastern Virginia Medical School, Norfolk, Virginia, USA.
Johnston
M
M
Birrer
M
M
Bos
T
T
D000074183:ATPases Associated with Diverse Cellular Activities; D048868:Adaptor Proteins, Signal Transducing; D001943:Breast Neoplasms / Q000235:genetics*; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D016758:Genes, jun; D006801:Humans; D060588:LIM Domain Proteins; D009687:Nuclear Proteins / Q000235:genetics; D046988:Proteasome Endopeptidase Complex; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics; D051742:Transcription Factor CHOP; D014157:Transcription Factors / Q000235:genetics; D014407:Tumor Cells, Cultured; D014746:Vimentin / Q000235:genetics; D016335:Zinc Fingers
D048868:Adaptor Proteins, Signal Transducing; D022762:CCAAT-Enhancer-Binding Proteins; D002352:Carrier Proteins; D019941:Cyclin-Dependent Kinase Inhibitor p16; C497249:DDIT3 protein, human; D060588:LIM Domain Proteins; D009687:Nuclear Proteins; C092282:PSMC5 protein, human; D016755:Proto-Oncogene Proteins c-jun; D019715:Tissue Inhibitor of Metalloproteinase-1; D014157:Transcription Factors; D014746:Vimentin; D051742:Transcription Factor CHOP; D046988:Proteasome Endopeptidase Complex; D000074183:ATPases Associated with Diverse Cellular Activities