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Cell Rep ; 9(3): 1047-60, 2014 Nov 06.
Article in English | MEDLINE | ID: mdl-25437559

ABSTRACT

Telomeric repeat binding factor 2 (TRF2), which plays a central role in telomere capping, is frequently increased in human tumors. We reveal here that TRF2 is expressed in the vasculature of most human cancer types, where it colocalizes with the Wilms' tumor suppressor WT1. We further show that TRF2 is a transcriptional target of WT1 and is required for proliferation, migration, and tube formation of endothelial cells. These angiogenic effects of TRF2 are uncoupled from its function in telomere capping. Instead, TRF2 binds and transactivates the promoter of the angiogenic tyrosine kinase platelet-derived growth factor receptor ß (PDGFRß). These findings reveal an unexpected role of TRF2 in neoangiogenesis and delineate a distinct function of TRF2 as a transcriptional regulator.


Subject(s)
Neovascularization, Pathologic/genetics , Promoter Regions, Genetic , Receptor, Platelet-Derived Growth Factor beta/genetics , Telomeric Repeat Binding Protein 2/metabolism , Animals , Cell Line, Tumor , Cell Movement/genetics , Cell Proliferation , DNA Damage , DNA Repair , Gene Knockout Techniques , Human Umbilical Vein Endothelial Cells/metabolism , Humans , Mice, Inbred C57BL , Neoplasms/blood supply , Neoplasms/pathology , Neovascularization, Pathologic/pathology , Protein Binding , Telomere/metabolism , Up-Regulation/genetics , WT1 Proteins/metabolism
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