Estrogen rapid action via protein complex formation involving ERalpha and Src.
This review provides insight into biomolecular knowledge regarding the non-genomic actions of estrogen in hormone-dependent breast cancer, particularly its role in the rapid stimulation of pathways that transmit signals to increase cell division or decrease programmed cell death. Until recently, attention to estrogenic effects focused primarily on events in the nucleus, where most estrogen receptors (ERalpha and beta) reside. However, a fraction of ERalpha associated with the cell membrane also participates in rapid estrogen-induced cell membrane-mediated events via formation of a protein complex with many signaling molecules, leading to activation of the mitogen-activated protein kinase and Akt signaling pathways. Understanding the mechanisms underlying these relationships, with the aim of abrogating specific steps, should lead to more targeted strategies to treat hormone-dependent breast cancer.
Song
Robert X-D
RX
Department of Internal Medicine, University of Virginia School of Medicine, Charlottesville, Virginia 22903, USA. rs5wf@virginia.edu
Zhang
Zhenguo
Z
Santen
Richard J
RJ
D048868:Adaptor Proteins, Signal Transducing / Q000502:physiology; D000818:Animals; D001943:Breast Neoplasms / Q000503:physiopathology; D022461:Caveolins / Q000502:physiology; D056970:Co-Repressor Proteins; D066246:ErbB Receptors / Q000502:physiology; D047628:Estrogen Receptor alpha / Q000502:physiology*; D047629:Estrogen Receptor beta / Q000502:physiology; D004967:Estrogens / Q000502:physiology*; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000502:physiology; D006801:Humans; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D017434:Protein Structure, Tertiary; D051057:Proto-Oncogene Proteins c-akt / Q000502:physiology; D043562:Receptors, G-Protein-Coupled / Q000502:physiology; D055765:Shc Signaling Adaptor Proteins; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1; D015534:Trans-Activators / Q000502:physiology; D014157:Transcription Factors; D019061:src-Family Kinases / Q000502:physiology*
D048868:Adaptor Proteins, Signal Transducing; D022461:Caveolins; D056970:Co-Repressor Proteins; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D004967:Estrogens; C438485:PELP1 protein, human; D043562:Receptors, G-Protein-Coupled; C528024:SHC1 protein, human; D055765:Shc Signaling Adaptor Proteins; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1; D015534:Trans-Activators; D014157:Transcription Factors; D019869:Phosphatidylinositol 3-Kinases; D066246:ErbB Receptors; D019061:src-Family Kinases; D051057:Proto-Oncogene Proteins c-akt; D020928:Mitogen-Activated Protein Kinases; D019206:GTP-Binding Protein alpha Subunits, Gi-Go