Involvement of Nuclear Receptor Coactivator SRC-1 in Estrogen-Dependent Cell Growth of MCF-7 Cells

Steroid hormones regulate cell growth and function through the transcriptional control of target genes by their cognate nuclear receptors. These receptors bind to ligands and associate with transcriptional cofactors to stimulate transcription. SRC-1, one of the nuclear receptor coactivators, is known to interact with nuclear receptors and enhance transactivation function in a ligand-dependent manner. In this study, to assess the function of SRC-1 in cell growth regulated by nuclear receptor ligands, we established a stable transformant cell line overexpressing human SRC-1 and studied the action of 17beta-estradiol (E(2)) on cell growth as well as the expression of E(2)-responsive genes in MCF-7 cells. We found that SRC-1 overexpression potentiates cell growth stimulated by E(2) in accordance with enhancement of transcriptional activation of exogenous and endogenous E(2)-responsive genes. These findings clearly indicate the importance of nuclear receptor coactivators for the activities of steroid/lipophilic vitamins in cell growth and gene expression.