Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2010-8-3
pubmed:abstractText
Synuclein gamma (SNCG), previously identified as a breast cancer-specific gene, is highly expressed in malignant cancer cells but not in normal epithelium. The molecular targets of SNCG during breast cancer progression have not been fully identified. Here we analyzed the effect of SNCG on stimulation of membrane-initiated estrogen signaling. While SNCG expression enhanced estrogen-induced activation of ERK1/2 and mammalian target of rapamycin, knockdown of endogenous SNCG decreased membrane-initiated estrogen signaling. SNCG functions as a molecular chaperone protein for estrogen receptor (ER)-alpha36, a membrane-based variant of ER-alpha. SNCG bound to ER-alpha36 in the presence and absence of functional molecular chaperone heat shock protein 90. Disruption of heat shock protein 90 with 17-AAG significantly reduced ER-alpha36 expression and membrane-initiated estrogen signaling. However, expression of SNCG prevented ER-alpha36 degradation and completely recovered 17-AAG-mediated down-regulation of estrogen signaling. The function of SNCG in ER-alpha36-mediated estrogen signaling is consistent with its ability to stimulate cell growth in response to estrogen. Expression of SNCG also renders tamoxifen resistance, which is consistent with the clinical observation on the association of ER-alpha36 expression and tamoxifen resistance. The present study indicates that ER-alpha36 is a new member of the ER-alpha family that mediates membrane-initiated estrogen signaling and that SNCG can replace the function of heat shock protein 90, chaperone ER-alpha36 activity, stimulate ligand-dependent cell growth, and render tamoxifen resistance.
pubmed:commentsCorrections
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pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
1525-2191
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
177
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
964-73
pubmed:dateRevised
2011-8-3
pubmed:meshHeading
pubmed-meshheading:20595634-Animals, pubmed-meshheading:20595634-Cell Proliferation, pubmed-meshheading:20595634-Estrogen Antagonists, pubmed-meshheading:20595634-Estrogen Receptor alpha, pubmed-meshheading:20595634-Estrogens, pubmed-meshheading:20595634-Extracellular Signal-Regulated MAP Kinases, pubmed-meshheading:20595634-HSP90 Heat-Shock Proteins, pubmed-meshheading:20595634-Mice, pubmed-meshheading:20595634-Mice, Nude, pubmed-meshheading:20595634-Molecular Chaperones, pubmed-meshheading:20595634-Neoplasm Transplantation, pubmed-meshheading:20595634-Protein Isoforms, pubmed-meshheading:20595634-RNA Interference, pubmed-meshheading:20595634-Signal Transduction, pubmed-meshheading:20595634-Tamoxifen, pubmed-meshheading:20595634-Tumor Cells, Cultured, pubmed-meshheading:20595634-gamma-Synuclein
pubmed:year
2010
pubmed:articleTitle
Synuclein gamma stimulates membrane-initiated estrogen signaling by chaperoning estrogen receptor (ER)-alpha36, a variant of ER-alpha.
pubmed:affiliation
Department of Radiation Medicine, The Feinstein Institute for Medical Research, New Hyde Park, New York, USA. eshi@lij.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't