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 ph enotype characterized not only by increased tumorigenicity but also by enha nced motility and invasion, The cellular phenotypic response to c-Jun overe xpression is likely due, at least in part, to altered patterns of gene expr ession. 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 expr ession of 588 different genes by comparative hybridization. By using this a pproach, we have identified a total of 21 upregulated or downregulated gene targets responsive to c-Jun overexpression. Interestingly, 8 of these gene s have been previously found associated with c-Jun or AP-I activity and the refore provide internal validation for this approach to target gene discove ry. The remaining 13 genes represent potential new c-Jun regulated target g enes, Genomic sequence information was available for 15 of the 21 genes ide ntified in this screen. Analysis of these genomic sequences revealed the pr esence of AP-I or AP-I-like sequences in 12 of the 15 genes examined. Consi stent with a direct mechanism of target regulation:by c-Jun, gel shift anal ysis of selected AP-I-containing promoter regions revealed elevated and spe cific binding by proteins present in nuclear extracts of c-Jun expressing M CF7 cells. Int. J. Cancer 88:180-190, 2000. (C) 2000 Wiley-Liss, Inc.