ASK1 (MAP3K5) as a potential therapeutic target in malignant fibrous histiocytomas with 12q14-q15 and 6q23 amplifications

Détails

ID Serval
serval:BIB_945F7DE9759D
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
ASK1 (MAP3K5) as a potential therapeutic target in malignant fibrous histiocytomas with 12q14-q15 and 6q23 amplifications
Périodique
Genes Chromosomes and Cancer
Auteur(s)
Chibon  F., Mariani  O., Derre  J., Mairal  A., Coindre  J. M., Guillou  L., Sastre  X., Pedeutour  F., Aurias  A.
ISSN
1045-2257 (Print)
Statut éditorial
Publié
Date de publication
2004
Volume
40
Numéro
1
Pages
32-37
Notes
PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't
Résumé
Malignant fibrous histiocytomas (MFHs) are aggressive tumors without any definable line of differentiation. We recently demonstrated that about 20% of them are characterized by high-level amplifications of the 12q14-q15 chromosome region, associated with either 1p32 or 6q23 band amplification. This genetic finding, very similar to that in well-differentiated liposarcomas, strongly suggests that these tumors actually correspond to undifferentiated liposarcomas. It also suggests that the lack of differentiation could be the consequence of amplification of target genes localized in the 1p32 or 6q23 bands. We report here the characterization by array CGH of the 6q23 minimal region of amplification. Our findings demonstrate that amplification and overexpression of ASK1 (MAP3K5), a gene localized in the 6q23 band and encoding a mitogen-activated protein kinase kinase kinase of the JNK-MAPK signaling pathway, could inhibit the adipocytic differentiation process of the tumor cells. Treatment of a cell line with specific inhibitors of ASK1 protein resulted in the bypass of the differentiation block and induction of a strong adipocytic differentiation. These observations indicate that ASK1 is a target for new therapeutic management of these aggressive tumors
Mots-clé
Abdominal Neoplasms/drug therapy/enzymology/genetics/Adipocytes/drug effects/Pathology/Aged/Cell Differentiation/Cell Line,Tumor/Chromosomes,Human,Pair 12/Chromosomes,Human,Pair 6/Enzyme Inhibitors/pharmacology/Female/Gene Amplification/Histiocytoma,Benign Fibrous/Humans/Liposarcoma/MAP Kinase Kinase Kinase 5/MAP Kinase Kinase Kinases/antagonists & inhibitors/physiology/MAP Kinase Signaling System/Male/Middle Aged/Nucleic Acid Hybridization/Retroperitoneal Neoplasms
Pubmed
Web of science
Création de la notice
29/01/2008 19:34
Dernière modification de la notice
03/03/2018 19:37
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