Linked Life Data

16261415

Source:http://linkedlifedata.com/resource/pubmed/id/16261415

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2005-11-1
pubmed:abstractText
We previously showed that conjugated linoleic acids (CLA) can inhibit transcriptional activation mediated by estrogen response elements (EREs) and that this activity can, at least in part, account for the reported anti-tumor effects of these compounds on breast cancer cells. Using estrogen receptor positive (ER+) MCF-7 cells, we now demonstrate that CLA inhibited both the transactivation of artificial reporter constructs driven by canonical EREs, and the expression of endogenous progesterone receptors, a gene which is transcriptionally regulated by estrogen through novel ER-binding sites. This inhibition was accompanied by downregulation of ER alpha expression and decreased ER alpha-ERE binding activity. These effects on ER alpha were not causally linked since transfection of an ER alpha expression plasmid in MCF-7 cells failed to antagonize CLA downregulation of ER alpha-ERE binding. Immunoprecipitation/Western blot studies revealed that CLA dose-dependently suppressed the degree of phosphorylation of ER alpha, a modification known to inhibit receptor-ERE interactions. As a mechanism that may account for this induced dephosphorylation of ER alpha in MCF-7, we found that CLA specifically stimulated protein phosphatase 2A (PP2A) activity. Experiments using the PP2A inhibitor okadaic acid (OA) showed that OA antagonized both the dephosphorylation effects of CLA on ER alpha and its inhibition of ER alpha-ERE binding. These results provide evidence that the anti-estrogenic activity of CLA is caused by inducing the dephosphorylation of ER alpha through stimulation of PP2A activity.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0167-6806
pubmed:author
pubmed:issnType
Print
pubmed:volume
94
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
161-9
pubmed:dateRevised
2007-12-3
pubmed:meshHeading
pubmed:year
2005
pubmed:articleTitle
Anti-estrogenic effects of conjugated linoleic acid through modulation of estrogen receptor phosphorylation.
pubmed:affiliation
Department of Gynecology and Obstetrics, Division of Research, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural