Linked Life Data

10218980

Source:http://linkedlifedata.com/resource/pubmed/id/10218980

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
1999-5-6
pubmed:abstractText
Oxytocin (OT) receptors (OTRs) mediate reproductive functions, including the initiation of labor and milk ejection. OTR messenger RNA levels are highly regulated, reaching the greatest concentration in the uterus at the end of gestation, and in the mammary gland during lactation. Factors directly effecting changes in OTR gene expression in the mammary gland are not known, so the present studies were done to elucidate possible regulators by characterizing the human OTR gene promoter and 5'-flanking sequence. By analyzing expression of promoter-luciferase constructs, we localized a region between -85 and -65 that was required for both basal and serum-induced expression in a mammary tumor cell line (Hs578T) that expresses inducible, endogenous OTRs. This DNA region contains an ets family target sequence (5'-GGA-3'), and a CRE/AP-1-like motif. The specific Ets factor binding to the OTR promoter was identified, by electrophoretic mobility immunoshift assays, to be GABP alpha/beta. Co-transfection of a -85 OTR/luciferase construct with vectors expressing GABP alpha and GABP beta1 had only a modest effect on expression, but cotransfection with GABP alpha/beta- with c-Fos/c-Jun-expressing plasmids resulted in an increase of almost 10-fold in luciferase activity. Mutation of either the GABP- or CRE-like binding sites obliterated the induction. These findings are consistent with the involvement of protein kinase C activity in serum induction of the endogenous gene in Hs578T cells. We showed the requirement for GABP alpha/beta and c-Fos/c-Jun in endogenous OTR gene expression, using oligonucleotide GABP and AP-1 binding decoys to inhibit serum-induced increases in 125I-labeled OT antagonist binding to Hs578T cells. Our work is the first characterization of the proximal promoter region of the human OTR gene, and it sets the stage for studying regulation of OTR expression in breast cells.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0013-7227
pubmed:author
pubmed:issnType
Print
pubmed:volume
140
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2268-79
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:10218980-Base Sequence, pubmed-meshheading:10218980-Binding Sites, pubmed-meshheading:10218980-Breast, pubmed-meshheading:10218980-Breast Neoplasms, pubmed-meshheading:10218980-DNA, pubmed-meshheading:10218980-DNA-Binding Proteins, pubmed-meshheading:10218980-Female, pubmed-meshheading:10218980-GA-Binding Protein Transcription Factor, pubmed-meshheading:10218980-Gene Expression, pubmed-meshheading:10218980-Genes, fos, pubmed-meshheading:10218980-Genes, jun, pubmed-meshheading:10218980-Humans, pubmed-meshheading:10218980-Molecular Sequence Data, pubmed-meshheading:10218980-Mutagenesis, pubmed-meshheading:10218980-Promoter Regions, Genetic, pubmed-meshheading:10218980-Receptors, Oxytocin, pubmed-meshheading:10218980-Recombinant Fusion Proteins, pubmed-meshheading:10218980-Sp1 Transcription Factor, pubmed-meshheading:10218980-Transcription Factor AP-1, pubmed-meshheading:10218980-Transcription Factors, pubmed-meshheading:10218980-Transfection, pubmed-meshheading:10218980-Tumor Cells, Cultured
pubmed:year
1999
pubmed:articleTitle
Identification of a GABP alpha/beta binding site involved in the induction of oxytocin receptor gene expression in human breast cells, potentiation by c-Fos/c-Jun.
pubmed:affiliation
Department of Obstetrics and Gynecology, University of Texas Medical Branch, Galveston 77555-1062, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.