Estrogens and cell-cycle regulation in breast cancer

Abstract Clinical and experimental data have established that the leading cause of sporadic female breast cancer is exposure to estrogens, predominantly 17β-estradiol. Recent advances in the understanding of cell-cycle control mechanisms have been applied to outline the molecular mechanisms through which estrogens regulate the cell cycle in cultured breast cancer cells, in particular, in MCF-7 cells. Here, we discuss how estrogens exert control over several key G 1 phase cell-cycle regulators, namely cyclin D1, Myc, Cdk2, Cdk4, Cdk inhibitors and Cdc25A. Although the molecular mechanisms underlying estrogenic regulation of G 1 phase regulators are far from clear, current evidence indicates that estrogens might regulate several key molecules required for S phase entry, this regulation being independent of cell-cycle transit per se .