Linked Life Data

17671179

Source:http://linkedlifedata.com/resource/pubmed/id/17671179

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
15
pubmed:dateCreated
2007-8-2
pubmed:abstractText
Aggressive fibromatosis (also called desmoid tumor) is a benign, locally invasive, soft tissue tumor composed of cells with mesenchymal characteristics. These tumors are characterized by increased levels of beta-catenin-mediated T-cell factor (TCF)-dependent transcriptional activation. We found that type 1 IFN signaling is activated in human and murine aggressive fibromatosis tumors and that the expression of associated response genes is regulated by beta-catenin. When mice deficient for the type 1 IFN receptor (Ifnar1-/-) were crossed with mice predisposed to developing aggressive fibromatosis tumors (Apc/Apc1638N), a significant decrease in aggressive fibromatosis tumor formation was observed compared with littermate controls, showing a novel role for type 1 IFN signaling in promoting tumor formation. Type 1 IFN activation inhibits cell proliferation but does not alter cell apoptosis or the level of beta-catenin-mediated TCF-dependent transcriptional activation in aggressive fibromatosis cell cultures. Thus, these changes cannot explain our in vivo results. Intriguingly, Ifnar1-/- mice have smaller numbers of mesenchymal progenitor cells compared with littermate controls, and treatment of aggressive fibromatosis cell cultures with IFN increases the proportion of cells that exclude Hoechst dye and sort to the side population, raising the possibility that type 1 IFN signaling regulates the number of precursor cells present that drive aggressive fibromatosis tumor formation and maintenance. This study identified a novel role for IFN type 1 signaling as a positive regulator of neoplasia and suggests that IFN treatment is a less than optimal therapy for this tumor type.
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0008-5472
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
67
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
7124-31
pubmed:dateRevised
2008-3-3
pubmed:meshHeading
pubmed-meshheading:17671179-Animals, pubmed-meshheading:17671179-Blotting, Western, pubmed-meshheading:17671179-Cell Proliferation, pubmed-meshheading:17671179-Cell Transformation, Neoplastic, pubmed-meshheading:17671179-Colony-Forming Units Assay, pubmed-meshheading:17671179-Female, pubmed-meshheading:17671179-Fibroblasts, pubmed-meshheading:17671179-Fibromatosis, Aggressive, pubmed-meshheading:17671179-Flow Cytometry, pubmed-meshheading:17671179-Genes, APC, pubmed-meshheading:17671179-Humans, pubmed-meshheading:17671179-Interferon-beta, pubmed-meshheading:17671179-Male, pubmed-meshheading:17671179-Mesenchymal Stem Cells, pubmed-meshheading:17671179-Mice, pubmed-meshheading:17671179-Neoplasm Invasiveness, pubmed-meshheading:17671179-Receptor, Interferon alpha-beta, pubmed-meshheading:17671179-Signal Transduction, pubmed-meshheading:17671179-T Cell Transcription Factor 1, pubmed-meshheading:17671179-Transcription, Genetic, pubmed-meshheading:17671179-Transgenes, pubmed-meshheading:17671179-Tumor Cells, Cultured, pubmed-meshheading:17671179-beta Catenin
pubmed:year
2007
pubmed:articleTitle
IFN-{beta} signaling positively regulates tumorigenesis in aggressive fibromatosis, potentially by modulating mesenchymal progenitors.
pubmed:affiliation
Program in Developmental and Stem Cell Biology, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't