Linked Life Data

11429412

Source:http://linkedlifedata.com/resource/pubmed/id/11429412

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
34
pubmed:dateCreated
2001-8-20
pubmed:abstractText
Estrogen receptors (ERs)(1) highly expressed by multiple myeloma (MM) cells and stimulation of estrogenic ligands leads to cell apoptosis. Interleukin (IL)-6 is a major growth factor in the pathogenesis of MM. However, little is known concerning the molecular consequences of ER activation on IL-6-regulated MM cell growth. Here we show that the ER agonist 17 beta-estradiol completely abolished IL-6-inducible MM cell proliferation. By contrast, the ER antagonist ICI 182,780 overcame the inhibitory effect of estrogen. Estrogen blocked STAT3 DNA binding and transactivation but failed to affect the mRNA expression of IL-6 receptor chains or activation of JAK2 and STAT3. Estrogen-activated ER did not associate directly with STAT3. Estrogen induced the mRNA expression of PIAS3 (protein inhibitor of activated STAT3) and increased PIAS3 physical association with STAT3, suggesting a possible mechanism of STAT3 inhibition requiring PIAS3 as a co-regulator modulating the cross-talk between ER and STAT3. These data directly demonstrate STAT3 to be a molecular participant in ER inhibition of the IL-6 signaling pathway in human MM cells and provides the molecular basis for the potential use of estrogenic ligands in the treatment of MM or other tumors where IL-6 has an autocrine or paracrine role.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
24
pubmed:volume
276
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
31839-44
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:11429412-Base Sequence, pubmed-meshheading:11429412-Carrier Proteins, pubmed-meshheading:11429412-DNA, pubmed-meshheading:11429412-DNA Primers, pubmed-meshheading:11429412-DNA-Binding Proteins, pubmed-meshheading:11429412-Estradiol, pubmed-meshheading:11429412-Humans, pubmed-meshheading:11429412-Interleukin-6, pubmed-meshheading:11429412-Multiple Myeloma, pubmed-meshheading:11429412-Receptor Cross-Talk, pubmed-meshheading:11429412-Receptors, Estrogen, pubmed-meshheading:11429412-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:11429412-STAT3 Transcription Factor, pubmed-meshheading:11429412-Signal Transduction, pubmed-meshheading:11429412-Trans-Activators, pubmed-meshheading:11429412-Transcriptional Activation, pubmed-meshheading:11429412-Tumor Cells, Cultured
pubmed:year
2001
pubmed:articleTitle
Activation of estrogen receptor blocks interleukin-6-inducible cell growth of human multiple myeloma involving molecular cross-talk between estrogen receptor and STAT3 mediated by co-regulator PIAS3.
pubmed:affiliation
Intramural Research Support Program, Science Applications International Corporation, National Cancer Institute, Frederick, Maryland 21702, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.