+ Site Statistics
+ Search Articles
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ PDF Full Text
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Translate
+ Recently Requested

Membrane initiated estrogen signaling in breast cancer

Membrane initiated estrogen signaling in breast cancer

Biology of Reproduction 75(1): 9-16

Recent research has focused on effects of the estrogen receptor acting at the level of the cell membrane in breast cancer. In this review we describe 17beta-estradiol (E2)-initiated membrane signaling pathways involving the activation of several kinases that contribute to the regulation of cell proliferation and prevention of apoptosis. Although classical concepts had assigned priority to the nuclear actions of estrogen receptor, recent studies document the additional importance of estrogen receptor residing in or near the plasma membrane. A small fraction of estrogen receptor is associated with the cell membrane and mediates the rapid effects of E2. Unlike classical growth factor receptors, such as insulin-like growth factor 1 receptor (IGF1R) and epidermal growth factor receptor (EGFR), estrogen receptor has no transmembrane and kinase domains and is known to initiate E2 rapid signals by forming a protein complex with many signaling molecules. The formation of the protein complex is a critical step, leading to the activation of the MAPK1/3 (also known as MAP kinase) and AKT1 (also known as Akt) pathways. 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.

(PDF emailed within 0-6 h: $19.90)

Accession: 013155674

Download citation: RISBibTeXText

PMID: 16571873

DOI: 10.1095/biolreprod.105.050070

Related references

Membrane-initiated steroid signaling action of estrogen and breast cancer. Seminars in Reproductive Medicine 25(3): 187-197, 2007

Membrane-bound estrogen receptor alpha initiated signaling is dynamin dependent in breast cancer cells. European Journal of Medical Research 23(1): 31, 2018

Early membrane initiated transcriptional effects of estrogens in breast cancer cells: First pharmacological evidence for a novel membrane estrogen receptor element (ERx). Steroids 77(10): 959-967, 2012

Nuclear and extranuclear-initiated estrogen receptor signaling crosstalk and endocrine resistance in breast cancer. Steroids 114: 41-47, 2016

Membrane estrogen signaling enhances tumorigenesis and metastatic potential of breast cancer cells via estrogen receptor-α36 (ERα36). Journal of Biological Chemistry 287(10): 7169-7181, 2012

A variant of estrogen receptor-a, hER-a36: Transduction of estrogen- and antiestrogen-dependent membrane-initiated mitogenic signaling. Proceedings of the National Academy of Sciences of the United States of America 103(24): 63-8, 2006

Synuclein gamma stimulates membrane-initiated estrogen signaling by chaperoning estrogen receptor (ER)-alpha36, a variant of ER-alpha. American Journal of Pathology 177(2): 964-973, 2011

Testosterone membrane-initiated action in breast cancer cells: Interaction with the androgen signaling pathway and EPOR. Molecular Oncology 4(2): 135-149, 2010

Estrogen signaling from the plasma membrane in breast cancer. Breast Cancer Research & Treatment 82(Supplement 1): S3, 2003

Membrane-initiated signaling of estrogen in the brain. Seminars in Reproductive Medicine 25(3): 165-177, 2007

Membrane-initiated estrogen signaling: oncogenic or impotent?. Expert Review of Endocrinology and Metabolism 7(4): 411-413, 2019

Membrane-initiated estrogen signaling in hypothalamic neurons. Molecular and Cellular Endocrinology 290(1-2): 14-23, 2008

A variant of estrogen receptor-{alpha}, hER-{alpha}36: transduction of estrogen- and antiestrogen-dependent membrane-initiated mitogenic signaling. Proceedings of the National Academy of Sciences of the United States of America 103(24): 9063-9068, 2006

Membrane-initiated estradiol signaling of epithelial-mesenchymal transition-associated mechanisms through regulation of tight junctions in human breast cancer cells. Hormones and Cancer 5(3): 161-173, 2015

Physiological consequences of membrane-initiated estrogen signaling in the brain. Frontiers in Bioscience 16: 1560-1573, 2011