Linked Life Data

19205871

Source:http://linkedlifedata.com/resource/pubmed/id/19205871

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2009-12-9
pubmed:abstractText
Estrogens play a crucial role in breast tumor growth, which is the rationale for the use of antiestrogens, such as tamoxifen, in women with estrogen receptor (ER)-alpha-positive breast cancer. However, hormone resistance is a major clinical problem. Altered growth factor signaling to the ERalpha pathway has been shown to be associated with the development of clinical resistance. We previously have identified a mutation that replaces arginine for lysine at residue 303 (K303R) of ERalpha, which confers hypersensitive growth in low levels of estrogen. To determine if the K303R mutation could participate in the evolution of hormone resistance, we generated MCF-7 breast cancer cells stably transfected with either wild-type (WT) or K303R ERalpha. We found that the mutation confers decreased sensitivity to tamoxifen in the presence of the growth factor heregulin, using anchorage-independent growth assays. K303R ERalpha-expressing cells were hypersensitive to growth factor signals. Our data suggest that phosphorylation of serine 305 within the hinge domain of ERalpha might play a key role in increasing ligand-independent activity of the mutant receptor. We hypothesize that the mutation adapts the receptor for enhanced bidirectional cross-talk with the HER2 growth factor receptor pathway, which then impacts on responsiveness to tamoxifen.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
1573-7217
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
119
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
71-85
pubmed:dateRevised
2011-3-10
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Growth factor-induced resistance to tamoxifen is associated with a mutation of estrogen receptor alpha and its phosphorylation at serine 305.
pubmed:affiliation
Department of Pharmaco-Biology, University of Calabria, Rende, Italy.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural