Cell proliferation regulated by estradiol receptor: Therapeutic implications

Estrogen receptor (ER) is a ligand-regulated transcription factor that controls human breast cancer cell proliferation. About 60-70% of human breast cancers express ER. In spite of major progress in the therapy of human breast cancer, many patients become resistant to pharmacologic treatments and develop metastatic breast tumors. Several mechanisms have been proposed to explain tumor progression and resistance to the therapies. However, the causes of hormone-dependent breast tumor progression as well as therapy resistance are still debated. An increasing body of evidence from our and other laboratories shows that in breast cancer cells, in addition to its classical transcriptional action, ER stimulates proliferative and anti-apoptotic signaling pathways in response to either ligand binding or growth factors. This discovery has led to the synthesis of new compounds specifically interfering in the rapid responses mediated by ER. It also suggests that the modalities currently in use for breast cancer treatment need to be reconsidered. (C) 2009 Elsevier Inc. All rights reserved.