Identification of cis- and trans-acting elements regulating calretinin expression in mesothelioma cells.

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Etat: Serval
Version: de l'auteur
ID Serval
serval:BIB_9227CBE1533D
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Identification of cis- and trans-acting elements regulating calretinin expression in mesothelioma cells.
Périodique
Oncotarget
Auteur(s)
Kresoja-Rakic J., Kapaklikaya E., Ziltener G., Dalcher D., Santoro R., Christensen B.C., Johnson K.C., Schwaller B., Weder W., Stahel R.A., Felley-Bosco E.
ISSN
1949-2553 (Electronic)
ISSN-L
1949-2553
Statut éditorial
Publié
Date de publication
2016
Peer-reviewed
Oui
Volume
7
Numéro
16
Pages
21272-21286
Langue
anglais
Résumé
Calretinin (CALB2) is a diagnostic marker for epithelioid mesothelioma. It is also a prognostic marker since patients with tumors expressing high calretinin levels have better overall survival. Silencing of calretinin decreases viability of epithelioid mesothelioma cells. Our aim was to elucidate mechanisms regulating calretinin expression in mesothelioma. Analysis of calretinin transcript and protein suggested a control at the mRNA level. Treatment with 5-aza-2'-deoxycytidine and analysis of TCGA data indicated that promoter methylation is not likely to be involved. Therefore, we investigated CALB2 promoter by analyzing ~1kb of genomic sequence surrounding the transcription start site (TSS) + 1 using promoter reporter assay. Deletion analysis of CALB2 proximal promoter showed that sequence spanning the -161/+80bp region sustained transcriptional activity. Site-directed analysis identified important cis-regulatory elements within this -161/+80bp CALB2 promoter. EMSA and ChIP assays confirmed binding of NRF-1 and E2F2 to the CALB2 promoter and siRNA knockdown of NRF-1 led to decreased expression of calretinin. Cell synchronization experiment showed that calretinin expression was cell cycle regulated with a peak of expression at G1/S phase. This study provides the first insight in the regulation of CALB2 expression in mesothelioma cells.
Pubmed
Web of science
Open Access
Oui
Création de la notice
02/02/2016 19:07
Dernière modification de la notice
08/05/2019 22:05
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