title: Membrane-initiated steroid signaling action of estrogen and breast cancer.
abstract: Although classical concepts had assigned priority to the nuclear-initiated steroid signaling pathway of estrogen receptor (ER), recent studies document that the ER also possesses the membrane-initiated steroid signaling (MISS) pathway. A small fraction of ER is associated with the cell membrane and mediates the rapid effects of estrogen. Unlike classical growth factor receptors, such as insulinlike growth factor 1 receptor and epidermal growth factor receptor, ER has no transmembrane and kinase domains. Instead, the initiating signals of MISS action of ER require a rapid formation of ER-centered protein complexes with many signaling molecules, leading to the activation of mitogen-activated protein kinase and Akt signaling pathways. In this review, we focus on the MISS action of ER and its role in the development of hormone resistance in breast cancer. A full understanding of the mechanisms, with the ultimate aim of abrogating specific steps, should lead to more targeted strategies for treatment of hormone-dependent breast cancer.
authors: Department of Internal Medicine, University of Virginia School of Medicine, Charlottesville, Virginia 22908, USA. rs5wf@virginia.edu
authors: Robert X-D
authors: RX
authors: Song
mesh_terms: D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D049109:Cell Proliferation; D019008:Drug Resistance, Neoplasm; D004967:Estrogens / Q000378:metabolism*; D005260:Female; D006801:Humans; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D011956:Receptors, Cell Surface / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000378:metabolism*; D015398:Signal Transduction; D014158:Transcription, Genetic
chemical_list: D018931:Antineoplastic Agents, Hormonal; D004967:Estrogens; D011956:Receptors, Cell Surface; D011960:Receptors, Estrogen