Microarray analysis of endoxifen concentration-dependent changes in gene expression in the presence of estrogen and physiologically relevant levels tamoxifen and its metabolites.

<p> (<b>A</b>) Venn diagram of genes whose expression levels were significantly altered by 1.5 fold or greater in MCF7 cells treated with 10 nM estrogen (E₂), 300 nM tamoxifen (TAM), 7 nM 4-hydroxy-tamoxifen (4HT) and 700 nM N-desmethyl-tamoxifen (NDT), plus indicated concentrations of endoxifen, relative to cells treated with all compounds minus endoxifen for 24 hours. (<b>B</b>) Venn diagram of genes detected to be regulated by the 100 nM and 20 nM endoxifen treatments. (<b>C</b>) Graph depicting the number of genes up-regulated (red) and down-regulated (green) by indicated treatments relative to E₂, TAM, 4HT and NDT treated cells. (<b>D</b>) Heat map depicting the hierarchical clustering of genes that were differentially expressed in at least one of the indicated treatment groups relative to E₂, TAM, 4HT and NDT treated cells and which had average fold-changes >3 standard deviations from all other genes in the comparison. Red indicates increased gene expression while green indicates decreased gene expression relative to vehicle treated controls.