A dedicated microarray for in-depth analysis of pre-mRNA splicing events: application to the study of genes involved in the response to targeted anticancer therapies.

Marine Pesson 1 Béatrice Eymin 2 Pierre De La Grange 3 Brigitte Simon 1 Laurent Corcos 1, *
* Auteur correspondant
1 Inserm U1078, équipe ECLA
Génétique, génomique fonctionnelle et biotechnologies (UMR 1078)
2 Equipe 2 - Bases Moléculaires de la Progression des Cancers du Poumon, Inserm U823
INSERM U823 - Institut d'oncologie/développement Albert Bonniot de Grenoble
Abstract : : Alternative pre-mRNA splicing (AS) widely expands proteome diversity through the combinatorial assembly of exons. The analysis of AS on a large scale, by using splice-sensitive microarrays, is a highly efficient method to detect the majority of known and predicted alternative transcripts for a given gene. The response to targeted anticancer therapies cannot easily be anticipated without prior knowledge of the expression, by the tumor, of target proteins or genes. To analyze, in depth, transcript structure and levels for genes involved in these responses, including AKT1-3, HER1-4, HIF1A, PIK3CA, PIK3R1-2, VEGFA-D and PIR, we engineered a dedicated gene chip with coverage of an average 185 probes per gene and, especially, exon-exon junction probes. As a proof of concept, we demonstrated the ability of such a chip to detect the effects of over-expressed SRSF2 RNA binding protein on the structure and abundance of mRNA products in H538 lung cancer cells conditionally over-expressing SRSF2. Major splicing changes were observed, including in HER1/EGFR pre-mRNA, which were also seen in human lung cancer samples over-expressing the SRSF2 protein. In addition, we showed that variations in HER1/EGFR pre-mRNA splicing triggered by SRSF2 overexpression in H358 cells resulted in a drop in HER1/EGFR protein level, which correlated with increased sensitivity to gefitinib, an EGFR tyrosine kinase inhibitor. We propose, therefore, that this novel tool could be especially relevant for clinical applications, with the aim to predict the response before treatment.
Type de document :
Article dans une revue
Molecular Cancer, BioMed Central, 2014, 13 (1), pp.9. 〈10.1186/1476-4598-13-9〉
Liste complète des métadonnées

Littérature citée [47 références]  Voir  Masquer  Télécharger

http://www.hal.inserm.fr/inserm-00935318
Contributeur : Ed. Bmc <>
Soumis le : jeudi 23 janvier 2014 - 13:15:21
Dernière modification le : jeudi 15 mars 2018 - 10:12:30
Document(s) archivé(s) le : jeudi 24 avril 2014 - 12:00:30

Fichiers

1476-4598-13-9.pdf
Fichiers éditeurs autorisés sur une archive ouverte

Identifiants

Collections

Citation

Marine Pesson, Béatrice Eymin, Pierre De La Grange, Brigitte Simon, Laurent Corcos. A dedicated microarray for in-depth analysis of pre-mRNA splicing events: application to the study of genes involved in the response to targeted anticancer therapies.. Molecular Cancer, BioMed Central, 2014, 13 (1), pp.9. 〈10.1186/1476-4598-13-9〉. 〈inserm-00935318〉

Partager

Métriques

Consultations de la notice

1145

Téléchargements de fichiers

203