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Cellular Oncology

, Volume 37, Issue 4, pp 253–267 | Cite as

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

  • 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
Article

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.

Keywords

Eukaryotic translation initiation eIFs Urinary bladder cancer Tumour marker 

Notes

Acknowledgments

We thank Theresa Eder, Veronika Rauch, Gertrude Zisser and Isolde Gunsch for their excellent technical assistance. We thank Mag. Karin Osibow for critical reading of our manuscript.

Conflict of interest

The authors declare that there is no conflicts of interest.

Supplementary material

13402_2014_181_Fig8_ESM.gif (902 kb)
Supplemental Fig. 1

Heat map displaying the gene ontology analysis results for ‘cell proliferation’ genes sorted by expression (GIF 902 kb)

13402_2014_181_MOESM1_ESM.tif (337 kb)
High resolution image (TIFF 337 kb)
13402_2014_181_MOESM2_ESM.pdf (3.1 mb)
Supplemental Table 1 (PDF 3166 kb)

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Copyright information

© International Society for Cellular Oncology 2014

Authors and Affiliations

  • Rita Spilka
    • 1
  • Christina Ernst
    • 2
  • Helmut Bergler
    • 3
  • Johannes Rainer
    • 4
  • Susanne Flechsig
    • 5
  • Alexander Vogetseder
    • 6
  • Eva Lederer
    • 2
  • Martin Benesch
    • 7
  • Andrea Brunner
    • 8
  • Stephan Geley
    • 4
  • Andreas Eger
    • 9
  • Felix Bachmann
    • 10
  • Wolfgang Doppler
    • 11
  • Peter Obrist
    • 1
  • Johannes Haybaeck
    • 2
    • 12
  1. 1.Laboratory of Pathology Dr. Obrist & Dr. Brunhuber OGZamsAustria
  2. 2.Institute of PathologyMedical University of GrazGrazAustria
  3. 3.Department of MicrobiologyUniversity of GrazGrazAustria
  4. 4.Division of Molecular PathophysiologyInnsbruck Medical UniversityInnsbruckAustria
  5. 5.Experimental Pharmacology & Oncology Berlin-Buch GmbHBerlin-BuchGermany
  6. 6.Division of Clinical PathologyUniversity Hospital ZurichZurichSwitzerland
  7. 7.Department of Pediatrics and Adolescent MedicineMedical University of GrazGrazAustria
  8. 8.Department of PathologyInnsbruck Medical UniversityInnsbruckAustria
  9. 9.University of Applied Sciences, Medical and Pharmaceutical BiotechnologyIMCKremsAustria
  10. 10.Basilea Pharmaceutica International Ltd.BaselSwitzerland
  11. 11.Division of Medical BiochemistryInnsbruck Medical UniversityInnsbruckAustria
  12. 12.Institute of PathologyMedical University of GrazGrazAustria

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