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eIF3a is over-expressed in urinary bladder cancer and influences its phenotype independent of translation initiation
- 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.
- Subjects :
- Male
Cancer Research
Pathology
medicine.medical_specialty
Eukaryotic Initiation Factor-3
Cell
Biology
In Vitro Techniques
Transcriptome
Eukaryotic translation
Cell Line, Tumor
Gene expression
medicine
Initiation factor
Humans
Aged
Gene knockdown
Cell growth
fungi
Cancer
General Medicine
medicine.disease
medicine.anatomical_structure
Oncology
Urinary Bladder Neoplasms
Protein Biosynthesis
Cancer research
Molecular Medicine
Female
Subjects
Details
- ISSN :
- 22113436
- Volume :
- 37
- Issue :
- 4
- Database :
- OpenAIRE
- Journal :
- Cellular oncology (Dordrecht)
- Accession number :
- edsair.doi.dedup.....4de923b30afcd65925fbbf7cdb7129df