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01-08-2014

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

Authors: Rita Spilka, Christina Ernst, Helmut Bergler, Johannes Rainer, Susanne Flechsig, Alexander Vogetseder, Eva Lederer, Martin Benesch, Andrea Brunner, Stephan Geley, Andreas Eger, Felix Bachmann, Wolfgang Doppler, Peter Obrist, Johannes Haybaeck

Published in: Cellular Oncology | Issue 4/2014

Abstract

Purpose

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.

Methods and results

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.

Conclusions

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.

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Title: eIF3a is over-expressed in urinary bladder cancer and influences its phenotype independent of translation initiation
Authors: Rita Spilka
Christina Ernst
Helmut Bergler
Johannes Rainer
Susanne Flechsig
Alexander Vogetseder
Eva Lederer
Martin Benesch
Andrea Brunner
Stephan Geley
Andreas Eger
Felix Bachmann
Wolfgang Doppler
Peter Obrist
Johannes Haybaeck
Publication date: 01-08-2014
Publisher: Springer Netherlands
Published in: Cellular Oncology / Issue 4/2014
Print ISSN: 2211-3428
Electronic ISSN: 2211-3436
DOI: https://doi.org/10.1007/s13402-014-0181-9

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