Titre
Induction of the interleukin-2/15 receptor beta-chain by the EWS-WT1 translocation product
Type
article
Institution
UNIL/CHUV/Unisanté + institutions partenaires
Périodique
Auteur(s)
Wong, J. C.
Auteure/Auteur
Lee, S. B.
Auteure/Auteur
Bell, M. D.
Auteure/Auteur
Reynolds, P. A.
Auteure/Auteur
Fiore, E.
Auteure/Auteur
Stamenkovic, I.
Auteure/Auteur
Truong, V.
Auteure/Auteur
Oliner, J. D.
Auteure/Auteur
Gerald, W. L.
Auteure/Auteur
Haber, D. A.
Auteure/Auteur
Liens vers les personnes
Liens vers les unités
ISSN
0950-9232
Statut éditorial
Publié
Date de publication
2002
Volume
21
Numéro
13
Première page
2009
Dernière page/numéro d’article
2019
Notes
PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S
Résumé
EWS-WT1 is a chimeric transcription factor resulting from fusion of the N-terminal domain of the Ewing sarcoma gene EWS to the three C-terminal zinc fingers of the Wilms tumor suppressor WT1. This translocation underlies desmoplastic small round cell tumor (DSRCT), which is noted for the abundance of reactive stroma surrounding islets of tumor cells, suggestive of paracrine signals contributing to tumor cell proliferation. Hybridization to high-density oligonucleotide microarrays can be used to identify targets of EWS-WT1. Expression of EWS-WT1 from a tetracycline-regulated promoter leads to the induction of growth-associated genes, of which the most remarkable is the beta-chain of the interleukin-2/15 receptor (IL-2/15Rbeta). Potent transcriptional activation by the chimeric protein maps to two bindings sites within the IL-2/15Rbeta promoter. Analysis of primary DSRCT tumor specimens demonstrates high levels of IL-2/15Rbeta within the tumor cells, along with expression of IL-2 and IL-15 by the abundant hyperplastic endothelial cells within the reactive stroma. Activation of this cytokine signaling pathway is consistent with the nuclear localization of its downstream effectors, phosphorylated STAT3 and STAT5. These observations suggest that the transcriptional induction of a cytokine receptor by a tumor-associated translocation product enables a proliferative response of epithelial cancer cells to ligands secreted by the surrounding stroma
Sujets
PID Serval
serval:BIB_F7E89FDA8001
PMID
Open Access
Oui
Date de création
2008-01-29T17:34:32.332Z
Date de création dans IRIS
2025-05-21T05:54:40Z