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eIF3a is over-expressed in urinary bladder cancer and influences its phenotype independent of translation initiation

Authors :
Martin Benesch
Alexander Vogetseder
Johannes Rainer
Andrea Brunner
Helmut Bergler
Susanne Flechsig
Rita Spilka
Felix Bachmann
Christina Ernst
Stephan Geley
E Lederer
Johannes Haybaeck
Peter Obrist
Andreas Eger
Wolfgang Doppler
Source :
Cellular oncology (Dordrecht). 37(4)
Publication Year :
2014

Abstract

The eukaryotic translation initiation factor (eIF) 3a, the largest subunit of the eIF3 complex, is a key functional entity in ribosome establishment and translation initiation. In the past, aberrant eIF3a expression has been linked to the pathology of various cancer types but, so far, its expression has not been investigated in transitional cell carcinomas. Here, we investigated the impact of eIF3 expression on urinary bladder cancer (UBC) cell characteristics and UBC patient survival. eIF3a expression was reduced through inducible knockdown in the UBC-derived cell lines RT112, T24, 5637 and HT1197. As a consequence of eIF3a down-regulation, UBC cell proliferation, clonogenic potential and motility were found to be decreased and, concordantly, UBC tumour cell growth rates were found to be impaired in xenotransplanted mice. Polysomal profiling revealed that reduced eIF3a levels increased the abundance of 80S ribosomes, rather than impairing translation initiation. Microarray-based gene expression and ontology analyses revealed broad effects of eIF3a knockdown on the transcriptome. Analysis of eIF3a expression in primary formalin-fixed paraffin embedded UBC samples of 198 patients revealed that eIF3a up-regulation corresponds to tumour grade and that high eIF3a expression corresponds to longer overall survival rates of patients with low grade tumours. From our results we conclude that eIF3a expression may have a profound effect on the UBC phenotype and, in addition, may serve as a prognostic marker for low grade UBCs.

Details

ISSN :
22113436
Volume :
37
Issue :
4
Database :
OpenAIRE
Journal :
Cellular oncology (Dordrecht)
Accession number :
edsair.doi.dedup.....4de923b30afcd65925fbbf7cdb7129df