Wild-type ALK and activating ALK-R1275Q and ALK-F1174L mutations upregulate Myc and initiate tumor formation in murine neural crest progenitor cells.

Détails

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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
Auteur⸱e⸱s
Montavon G., Jauquier N., Coulon A., Peuchmaur M., Flahaut M., Bourloud K.B., Yan P., Delattre O., Sommer L., Joseph J.M., Janoueix-Lerosey I., Gross N., Mühlethaler-Mottet A.
ISSN
1949-2553 (Electronic)
ISSN-L
1949-2553
Statut éditorial
Publié
Date de publication
2014
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 8:39
Dernière modification de la notice
21/11/2022 8:20
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