title: eIF3a is over-expressed in urinary bladder cancer and influences its phenotype independent of translation initiation.
abstract: OBJECTIVE
  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.
  
  
  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.
authors: Laboratory of Pathology Dr. Obrist & Dr. Brunhuber OG, Klostergasse 1, 6511, Zams, Tyrol, Austria, rita.spilka@student.i-med.ac.at.
authors: Rita
authors: R
authors: Spilka
authors: Christina
authors: C
authors: Ernst
authors: Helmut
authors: H
authors: Bergler
authors: Johannes
authors: J
authors: Rainer
authors: Susanne
authors: S
authors: Flechsig
authors: Alexander
authors: A
authors: Vogetseder
authors: Eva
authors: E
authors: Lederer
authors: Martin
authors: M
authors: Benesch
authors: Andrea
authors: A
authors: Brunner
authors: Stephan
authors: S
authors: Geley
authors: Andreas
authors: A
authors: Eger
authors: Felix
authors: F
authors: Bachmann
authors: Wolfgang
authors: W
authors: Doppler
authors: Peter
authors: P
authors: Obrist
authors: Johannes
authors: J
authors: Haybaeck
mesh_terms: D000368:Aged; D045744:Cell Line, Tumor; D039621:Eukaryotic Initiation Factor-3 / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D014176:Protein Biosynthesis / Q000235:genetics / Q000502:physiology*; D001749:Urinary Bladder Neoplasms / Q000235:genetics / Q000378:metabolism*
chemical_list: C105988:EIF3A protein, human; D039621:Eukaryotic Initiation Factor-3