Linked Life Data

18314487

Source:http://linkedlifedata.com/resource/pubmed/id/18314487

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2008-3-3
pubmed:abstractText
Pygopus is a component of the T-cell factor/beta-catenin transcriptional complex essential for activation of Wnt target genes and is also required for cell regulation in the absence of Wnt signaling. Human Pygopus2 (hPygo2) is overexpressed in a high proportion of breast and epithelial ovarian malignant tumors and is required for the growth of several cell lines derived from these carcinomas. The mechanisms regulating hPygo2 gene activation, however, are unknown. Here, we have determined cis- and trans-interacting factors responsible for hPygo2 expression in cancer. The minimal region required for a maximal 109-fold activation of the hPygo2 promoter in MCF-7 breast cancer cells is 48 bp upstream of the start of transcription. Within 25 bp of the transcriptional start, there are two overlapping tandem Ets transcription factor-binding sites, which are critical for hPygo2 promoter activity. In vitro DNA pull-down assays and proteomic analyses identified the Ets family members Elk-1 and E74-like factor-1 (Elf-1) as potential hPygo2 promoter binding factors, whereas in vivo chromatin immunoprecipitation assays verified that only Elf-1 specifically bound to the hPygo2 promoter in MCF-7 cells. Modulation of elf-1 in MCF-7 cells by silencing via RNA interference or overexpression caused a corresponding decrease or increase, respectively, in hPygo2 promoter activity. Overexpression of Elf-1 in HeLa cells, in which Elf-1 is expressed at a lower level than in MCF-7 cells, caused a 4-fold increase in endogenous hPygo2 mRNA levels. These results provide new evidence that Elf-1 is involved in transcriptional activation of hPygo2. Like hPygo2, previous studies implicated Elf-1 in breast and ovarian cancer and our present findings suggest that the oncogenic requirement of hPygo2 is fulfilled, in part, by Elf-1.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
1541-7786
pubmed:author
pubmed:issnType
Print
pubmed:volume
6
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
259-66
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:18314487-Amino Acid Sequence, pubmed-meshheading:18314487-Base Sequence, pubmed-meshheading:18314487-Binding Sites, pubmed-meshheading:18314487-Cell Line, Tumor, pubmed-meshheading:18314487-Gene Expression Regulation, Neoplastic, pubmed-meshheading:18314487-Humans, pubmed-meshheading:18314487-Intracellular Signaling Peptides and Proteins, pubmed-meshheading:18314487-Molecular Sequence Data, pubmed-meshheading:18314487-Nuclear Proteins, pubmed-meshheading:18314487-Peptides, pubmed-meshheading:18314487-Promoter Regions, Genetic, pubmed-meshheading:18314487-Protein Binding, pubmed-meshheading:18314487-Proteomics, pubmed-meshheading:18314487-Proto-Oncogene Proteins c-ets, pubmed-meshheading:18314487-Transcription Factors, pubmed-meshheading:18314487-Transcriptional Activation
pubmed:year
2008
pubmed:articleTitle
Oncogenic activation of the human Pygopus2 promoter by E74-like factor-1.
pubmed:affiliation
Terry Fox Cancer Research Laboratories, Division of Basic Medical Sciences, Faculty of Medicine, Memorial University of Newfoundland, St John's, Newfoundland, Canada.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't