Linked Life Data

18798221

Source:http://linkedlifedata.com/resource/pubmed/id/18798221

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2008-11-13
pubmed:abstractText
The beta-catenin/TCF4/p300 pathway is involved in early signalling for trans-differentiation towards the morular phenotype of endometrial carcinoma cells, but little is known about the upstream regulators. Here we show that transcription factor early growth response 1 (Egr1) acts as an initial mediator through up-regulating the expression of TCF4 and p300. In an endometrial carcinoma cell line with abundant oestrogen receptor alpha, Egr1 expression at both mRNA and protein levels was significantly increased by serum and 17beta-oestradiol stimuli. Serum-stimulated cells also showed increased expression of TCF4 and p300, while inhibition of Egr1 by specific siRNAs resulted in decreased expression. Transfection of Egr1 led to transactivation of TCF4 as well as p300 genes, through specific binding to a promoter region, and thus in turn resulted in nuclear accumulation of beta-catenin mediated by the up-regulating TCF4. The overexpression also caused inhibition of beta-catenin/TCF4/p300-mediated transcription, probably through sequestration of p300. Egr1 promoter activity was increased by serum but not 17beta-oestradiol, in contrast to the marked repression associated with TCF4, p300, and Egr1 itself, indicating that the regulation involves several feedback loops. In clinical samples, cells immunopositive for nuclear Egr1, as well as beta-catenin and TCF4, were found to be sporadically distributed in glandular components of endometrial carcinoma with morules. A significant positive correlation between nuclear beta-catenin and TCF4 was observed, but no such link was evident for Egr1, probably due to the existence of negative feedback regulation. Together, these data indicate that Egr1 may participate in modulation of the beta-catenin/TCF4/p300 signalling pathway as an initial event during trans-differentiation of endometrial carcinoma cells, through its impact on several signalling networks.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1096-9896
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
216
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
521-32
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:18798221-Base Sequence, pubmed-meshheading:18798221-Cell Line, Tumor, pubmed-meshheading:18798221-E1A-Associated p300 Protein, pubmed-meshheading:18798221-Early Growth Response Protein 1, pubmed-meshheading:18798221-Endometrial Neoplasms, pubmed-meshheading:18798221-Estrogen Receptor alpha, pubmed-meshheading:18798221-Female, pubmed-meshheading:18798221-Gene Expression, pubmed-meshheading:18798221-Gene Expression Regulation, Neoplastic, pubmed-meshheading:18798221-Humans, pubmed-meshheading:18798221-Immunohistochemistry, pubmed-meshheading:18798221-Molecular Sequence Data, pubmed-meshheading:18798221-Promoter Regions, Genetic, pubmed-meshheading:18798221-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:18798221-Statistics, Nonparametric, pubmed-meshheading:18798221-TCF Transcription Factors, pubmed-meshheading:18798221-Transcription Factor 7-Like 2 Protein, pubmed-meshheading:18798221-Transcriptional Activation, pubmed-meshheading:18798221-Transfection, pubmed-meshheading:18798221-Up-Regulation, pubmed-meshheading:18798221-beta Catenin
pubmed:year
2008
pubmed:articleTitle
Transcription factor Egr1 acts as an upstream regulator of beta-catenin signalling through up-regulation of TCF4 and p300 expression during trans-differentiation of endometrial carcinoma cells.
pubmed:affiliation
Department of Pathology, Kitasato University School of Medicine, 1-15-1 Kitasato, Sagamihara, Kanagawa 228-8555, Japan. msaegusa@med.kitasato-u.ac.jp
pubmed:publicationType
Journal Article