title: Translational control is a major contributor to hypoxia induced gene expression.
abstract: OBJECTIVE
  Hypoxia is a common feature of solid tumors that is associated with an aggressive phenotype, resistance to therapy and poor prognosis. Major contributors to these adverse effects are the transcriptional program activated by the HIF family of transcription factors as well as the translational response mediated by PERK-dependent phosphorylation of eIF2α and inhibition of mTORC1 activity. In this study we determined the relative contribution of both transcriptional and translational responses to changes in hypoxia induced gene expression.
  
  
  METHODS
  Total and efficiently translated (polysomal) mRNA was isolated from DU145 prostate carcinoma cells that were exposed for up to 24 h of hypoxia (<0.02% O(2)). Changes in transcription and translation were assessed using affymetrix microarray technology.
  
  
  RESULTS
  Our data reveal an unexpectedly large contribution of translation control on both induced and repressed gene expression at all hypoxic time points, particularly during acute hypoxia (2-4 h). Gene ontology analysis revealed that gene classes like transcription and signal transduction are stimulated by translational control whereas expression of genes involved in cell growth and protein metabolism are repressed during hypoxic conditions by translational control.
  
  
  CONCLUSIONS
  Our data indicate that translation influences gene expression during hypoxia on a scale comparable to that of transcription.
authors: Department of Radiation Oncology (Maastro Lab), Maastricht University, The Netherlands.
authors: Twan
authors: T
authors: van den Beucken
authors: Michael G
authors: MG
authors: Magagnin
authors: Barry
authors: B
authors: Jutten
authors: Renaud
authors: R
authors: Seigneuric
authors: Philippe
authors: P
authors: Lambin
authors: Marianne
authors: M
authors: Koritzinsky
authors: Bradly G
authors: BG
authors: Wouters
mesh_terms: D015687:Cell Hypoxia / Q000235:genetics*; D045744:Cell Line, Tumor; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D011471:Prostatic Neoplasms / Q000235:genetics*; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction; D014407:Tumor Cells, Cultured
chemical_list: D012333:RNA, Messenger