Figure 4.

Genes 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).