High expression of the RNA-binding protein RBPMS2 in gastrointestinal stromal tumors.

Détails

ID Serval
serval:BIB_CD08A4F9AD89
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
High expression of the RNA-binding protein RBPMS2 in gastrointestinal stromal tumors.
Périodique
Experimental and Molecular Pathology
Auteur(s)
Hapkova I., Skarda J., Rouleau C., Thys A., Notarnicola C., Janikova M., Bernex F., Rypka M., Vanderwinden J.M., Faure S., Vesely J., de Santa Barbara P.
ISSN
1096-0945 (Electronic)
ISSN-L
0014-4800
Statut éditorial
Publié
Date de publication
2013
Peer-reviewed
Oui
Volume
94
Numéro
2
Pages
314-321
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't Publication Status: ppublish
Résumé
Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms of the gastrointestinal tract and are often associated with KIT or PDGFRA gene mutations. GIST cells might arise from the interstitial cells of Cajal (ICCs) or from a mesenchymal precursor that is common to ICCs and smooth muscle cells (SMCs). Here, we analyzed the mRNA and protein expression of RNA-Binding Protein with Multiple Splicing-2 (RBPMS2), an early marker of gastrointestinal SMC precursors, in human GISTs (n=23) by in situ hybridization, quantitative RT-PCR analysis and immunohistochemistry. The mean RBPMS2 mRNA level in GISTs was 42-fold higher than in control gastrointestinal samples (p<0.001). RBPMS2 expression was not correlated with KIT and PDGFRA expression levels, but was higher in GISTs harboring KIT mutations than in tumors with wild type KIT and PDGFRA or in GISTs with PDGFRA mutations that were characterized by the lowest RBPMS2 levels. Moreover, RBPMS2 levels were 64-fold higher in GIST samples with high risk of aggressive behavior than in adult control gastrointestinal samples and 6.2-fold higher in high risk than in low risk GIST specimens. RBPMS2 protein level was high in 87% of the studied GISTs independently of their histological classification. Finally, by inhibiting the KIT signaling pathway in GIST882 cells, we show that RBPMS2 expression is independent of KIT activation. In conclusion, RBPMS2 is up-regulated in GISTs compared to normal adult gastrointestinal tissues, indicating that RBPMS2 might represent a new diagnostic marker for GISTs and a potential target for cancer therapy.
Mots-clé
Adult, Aged, Amino Acid Sequence, Cell Line, Tumor, Female, Gastrointestinal Neoplasms/genetics, Gastrointestinal Neoplasms/metabolism, Gastrointestinal Stromal Tumors/genetics, Gastrointestinal Stromal Tumors/metabolism, Gastrointestinal Tract/metabolism, Gene Expression, HEK293 Cells, Humans, Male, Middle Aged, Molecular Sequence Data, Mutation, Proto-Oncogene Proteins c-kit/antagonists & inhibitors, Proto-Oncogene Proteins c-kit/genetics, RNA, Messenger/genetics, RNA, Messenger/metabolism, RNA-Binding Proteins/biosynthesis, RNA-Binding Proteins/metabolism, Receptor, Platelet-Derived Growth Factor alpha/genetics, Signal Transduction
Pubmed
Web of science
Création de la notice
06/06/2013 15:49
Dernière modification de la notice
03/03/2018 21:29
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