Figure 4From: Genes regulated by estrogen in breast tumor cells in vitro are similarly regulated in vivoin tumor xenografts and human breast tumorsGenes induced by E2 in vitro are enriched for transcriptional targets of Myc. A conditional Myc-estrogen receptor (Myc-ER) fusion protein was used to induce Myc transcriptional activity. Conditional activation of Myc occurs upon stimulation with the anti-estrogen 4-hydroxytamoxifen (OHT). Gene expression profiles were taken of primary human fibroblasts with Myc-ER to identify transcriptional targets of Myc [22] (CHX, cycloheximide). (a) Enrichment of Myc targets (p < 0.01) within each of the distinct clusters of estrogen-regulated genes (Figure 1). Values indicating significance of overlap (p < 0.05) between two given genes sets are in bold. (b) Expression data matrix for cluster B and C genes that were also represented in the Myc-ER dataset, alongside the corresponding values in both the Myc-ER dataset and in a profile dataset from [26] of human fibroblasts grown in high and low serum conditions, in which Myc is up-regulated in the high serum group. Myc targets (p < 0.01) are listed (asterisk indicates has predicted Myc TF site in promoter region; italics indicate cell cycle gene from [13]). (c) GSEA of the cluster B genes against the overall ranking of genes according to similarity with myc mRNA expression in a compendium of tumor profiles from breast and 10 other tissues types from [24]. (d) GSEA results for estrogen-regulated gene clusters A to H, genes induced by Myc-ER+OHT in fibroblasts (p < 0.01), and cell cycle genes [13], against gene rankings by Myc correlation in four different datasets (clusters A to H, FWER p, Myc and cell cycle, nominal p).Back to article page