Wild-type ALK and activating ALK-R1275Q and ALK-F1174L mutations upregulate Myc and initiate tumor formation in murine neural crest progenitor cells.
Détails
Télécharger: BIB_9D95D6FECC81.P001.pdf (1577.23 [Ko])
Etat: Public
Version: Final published version
Licence: Non spécifiée
Etat: Public
Version: Final published version
Licence: Non spécifiée
ID Serval
serval:BIB_9D95D6FECC81
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Wild-type ALK and activating ALK-R1275Q and ALK-F1174L mutations upregulate Myc and initiate tumor formation in murine neural crest progenitor cells.
Périodique
Oncotarget
ISSN
1949-2553 (Electronic)
ISSN-L
1949-2553
Statut éditorial
Publié
Date de publication
2014
Peer-reviewed
Oui
Volume
5
Numéro
12
Pages
4452-4466
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov'tPublication Status: ppublish
Résumé
The anaplastic lymphoma kinase (ALK) gene is overexpressed, mutated or amplified in most neuroblastoma (NB), a pediatric neural crest-derived embryonal tumor. The two most frequent mutations, ALK-F1174L and ALK-R1275Q, contribute to NB tumorigenesis in mouse models, and cooperate with MYCN in the oncogenic process. However, the precise role of activating ALK mutations or ALK-wt overexpression in NB tumor initiation needs further clarification. Human ALK-wt, ALK-F1174L, or ALK-R1275Q were stably expressed in murine neural crest progenitor cells (NCPC), MONC-1 or JoMa1, immortalized with v-Myc or Tamoxifen-inducible Myc-ERT, respectively. While orthotopic implantations of MONC- 1 parental cells in nude mice generated various tumor types, such as NB, osteo/ chondrosarcoma, and undifferentiated tumors, due to v-Myc oncogenic activity, MONC-1-ALK-F1174L cells only produced undifferentiated tumors. Furthermore, our data represent the first demonstration of ALK-wt transforming capacity, as ALK-wt expression in JoMa1 cells, likewise ALK-F1174L, or ALK-R1275Q, in absence of exogenous Myc-ERT activity, was sufficient to induce the formation of aggressive and undifferentiated neural crest cell-derived tumors, but not to drive NB development. Interestingly, JoMa1-ALK tumors and their derived cell lines upregulated Myc endogenous expression, resulting from ALK activation, and both ALK and Myc activities were necessary to confer tumorigenic properties on tumor-derived JoMa1 cells in vitro.
Mots-clé
ALK, neuroblastoma, Myc, tumorigenesis, differentiation, RECEPTOR TYROSINE KINASE, STEM-CELLS, NEUROBLASTOMA PREDISPOSITION, ONCOGENIC MUTATIONS, EXPRESSION, DIFFERENTIATION, AMPLIFICATION, GENE, INDUCTION, APOPTOSIS
Pubmed
Web of science
Création de la notice
08/09/2014 9:39
Dernière modification de la notice
13/01/2024 8:09