Estrogen-Regulated Gene Networks in Human Breast Cancer Cells: Involvement of E2F1 in the Regulation of Cell Proliferation

摘要: Estrogens generally stimulate the proliferation of estrogen receptor (ER)-containing breast cancer cells, but they also suppress some ER-positive tumors. Using a genome-wide analysis gene expression in two human cell lines that differ their proliferative response to estrogen, we sought identify genes involved estrogen-regulated proliferation. To this end, compared transcriptional profiles MCF-7 and MDA-MB-231ER+ which have directionally opposite 17beta-estradiol (E2)-dependent patterns, cells being stimulated 231ER+ suppressed by E2. We identified set approximately 70 regulated E2 both with most hormone an fashion. variety bioinformatics approaches, found E2F binding site be overrepresented potential regulatory regions many cycle-related inhibited cells. Biochemical analyses confirmed E2F1 downstream target were increased decreased upon treatment. Furthermore, RNA interference-mediated knockdown blocked regulation resulted loss These results demonstrate E2F1, subsequently its genes, is critical for program these profiling combined bioinformatic transcription factor enrichment can key components associated nuclear hormonal important cellular functions.