scholarly journals The role of Shc and insulin-like growth factor 1 receptor in mediating the translocation of estrogen receptor α to the plasma membrane

2004 ◽  
Vol 101 (7) ◽  
pp. 2076-2081 ◽  
Author(s):  
Robert X. Song ◽  
Christopher J. Barnes ◽  
Zhenguo Zhang ◽  
Yongde Bao ◽  
Rakesh Kumar ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Plasma Membrane ◽  
Growth Factor ◽  
Estrogen Receptor Α ◽  
Insulin Like Growth Factor

Role of receptor complexes in the extranuclear actions of estrogen receptor α in breast cancer

2006 ◽  
Vol 13 (Supplement_1) ◽  
pp. S3-S13 ◽  
Author(s):  
Robert X-D Song ◽  
Ping Fan ◽  
Wei Yue ◽  
Yucai Chen ◽  
Richard J Santen
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Plasma Membrane ◽  
Growth Factor ◽  
Growth Factor Receptor ◽  
Adaptor Proteins ◽  
Estrogen Receptor Α ◽  
Mitogen Activated Protein Kinase ◽  
Receptor Complexes

Our recent studies have examined the role of various receptor complexes in the mediation of rapid, extranuclear effects of estradiol. This review describes 17β-estradiol (E2)-initiated extranuclear signaling pathways, which involve the insulin-like growth factor 1 receptor (IGF-1R) and epidermal growth factor receptor (EGFR) and result in the activation of several kinase cascades. The biologic results of these effects are the enhancement of cell proliferation and diminution of programmed cell death (apoptosis). Until recently, most studies assigned priority to the nuclear transcriptional actions of estrogen receptor α (ERα). Present investigative emphasis focuses on the additional importance of ERα residing in or near the plasma membrane. A small fraction of ERα is associated with the cell membrane and mediates the rapid effects of E2. Unlike classical growth factor receptors, such as IGF-1R and EGFR, ERα has no transmembrane and kinase domains and is known to initiate E2 rapid signals by forming protein/protein complexes with many signaling molecules. Our recent studies demonstrate that the IGF-1R is involved in tethering ERα to the plasma membrane, in activating the EGFR, and in the initiation of mitogen-activated protein kinase and phosphoinositide 3-kinase signaling. The formation of a multi-protein complex containing these receptors as well as adaptor proteins is a critical step in this process. A full understanding of the mechanisms underlying these relationships with the ultimate aim of abrogating specific steps, should lead to more targeted strategies for treatment of hormone-dependent breast cancer.

scholarly journals Palmitoylation-dependent Estrogen Receptor α Membrane Localization: Regulation by 17β-Estradiol

2005 ◽  
Vol 16 (1) ◽  
pp. 231-237 ◽  
Author(s):  
Filippo Acconcia ◽  
Paolo Ascenzi ◽  
Alessio Bocedi ◽  
Enzo Spisni ◽  
Vittorio Tomasi ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Estrogen Receptor ◽  
Plasma Membrane ◽  
Estrogen Receptor Α ◽  
Membrane Localization ◽  
Target Cells ◽  
Dependent Manner ◽  
Caveolin 1 ◽  
17Β Estradiol

A fraction of the nuclear estrogen receptor α (ERα) is localized to the plasma membrane region of 17β-estradiol (E2) target cells. We previously reported that ERα is a palmitoylated protein. To gain insight into the molecular mechanism of ERα residence at the plasma membrane, we tested both the role of palmitoylation and the impact of E2 stimulation on ERα membrane localization. The cancer cell lines expressing transfected or endogenous human ERα (HeLa and HepG2, respectively) or the ERα nonpalmitoylable Cys447Ala mutant transfected in HeLa cells were used as experimental models. We found that palmitoylation of ERα enacts ERα association with the plasma membrane, interaction with the membrane protein caveolin-1, and nongenomic activities, including activation of signaling pathways and cell proliferation (i.e., ERK and AKT activation, cyclin D1 promoter activity, DNA synthesis). Moreover, E2 reduces both ERα palmitoylation and its interaction with caveolin-1, in a time- and dose-dependent manner. These data point to the physiological role of ERα palmitoylation in the receptor localization to the cell membrane and in the regulation of the E2-induced cell proliferation.

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