Linked Life Data

15976008

Source:http://linkedlifedata.com/resource/pubmed/id/15976008

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
2005-10-26
pubmed:abstractText
Breast cancer cell growth may be stimulated by 17beta-estradiol (E2) or growth factors like epidermal growth factor (EGF). However, tumors typically depend on only one of these pathways and may overexpress either estrogen receptor (ER) or EGF receptor (EGFR) and related family members. Tumors overexpressing EGFR are more aggressive than those expressing ER. Intracellular mediators of these growth-stimulatory pathways are not completely defined, but one potential common mediator of EGF and E2 signaling is the transcription factor signal transducer and activator of transcription 5 (STAT5). To investigate the role of STAT5 in potential crosstalk between E2 and EGF, MDA-MB231 and SKBr3 breast cancer cells, which are ER-negative and overexpress human EGF family receptors, were used. Introduction of ERalpha and treatment with E2 decreased EGF-induced tyrosine phosphorylation of STAT5b, basal and EGF-induced STAT5-mediated transcription, and EGF-stimulated DNA synthesis in these cells. Suppressive effects of E2-EpsilonRalpha were specific for STAT5, as EGF stimulation of MAPK was unaffected. Deletion/mutation analysis of ERalpha demonstrated that the DNA-binding domain was insufficient, and that the ligand-binding domain was required for these responses. ERalpha transcriptional activity was not necessary for suppression of STAT5 activity. Overexpression of c-Src did not prevent suppression of STAT5 activity by E2 and ERalpha. However, ERalpha did prevent basal increases in STAT5 activity with overexpressed c-Src. In the context of human EGF receptor family overexpression, E2-ER opposes EGF signaling by regulating STAT5 activity. STAT5 may be a crucial point of signaling for both E2 and growth factors in breast cancer cells, allowing targeted therapy for many types of breast tumors.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0888-8809
pubmed:author
pubmed:issnType
Print
pubmed:volume
19
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2660-70
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:15976008-Breast Neoplasms, pubmed-meshheading:15976008-Bromodeoxyuridine, pubmed-meshheading:15976008-Enzyme Activation, pubmed-meshheading:15976008-Epidermal Growth Factor, pubmed-meshheading:15976008-Estradiol, pubmed-meshheading:15976008-Estrogen Receptor alpha, pubmed-meshheading:15976008-Genes, Reporter, pubmed-meshheading:15976008-Humans, pubmed-meshheading:15976008-Luciferases, pubmed-meshheading:15976008-Mitogen-Activated Protein Kinase Kinases, pubmed-meshheading:15976008-Phosphorylation, pubmed-meshheading:15976008-Proto-Oncogene Proteins c-akt, pubmed-meshheading:15976008-Receptor, Epidermal Growth Factor, pubmed-meshheading:15976008-STAT5 Transcription Factor, pubmed-meshheading:15976008-Signal Transduction, pubmed-meshheading:15976008-Transcription, Genetic, pubmed-meshheading:15976008-Transfection, pubmed-meshheading:15976008-Tumor Cells, Cultured, pubmed-meshheading:15976008-src-Family Kinases
pubmed:year
2005
pubmed:articleTitle
Estrogen negatively regulates epidermal growth factor (EGF)-mediated signal transducer and activator of transcription 5 signaling in human EGF family receptor-overexpressing breast cancer cells.
pubmed:affiliation
Department of Microbiology, University of Virginia, Charlottesville, Virginia 22908, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural