title: The transcriptional response of mammalian cancer cells to irradiation is dominated by a cell cycle signature which is strongly attenuated in non-cancer cells and tissues.
abstract: OBJECTIVE
  Our goal was to identify genes showing a general transcriptional response to irradiation in mammalian cells and to analyze their response in function of dose, time and quality of irradiation and of cell type.
  
  
  METHODS
  We used a modified MIAME (Minimal Information About Microarray Experiments) protocol to import microarray data from 177 different irradiation conditions in the Radiation Genes database and performed cut-off-based selections and hierarchical gene clustering.
  
  
  RESULTS
  We identified a set of 29 genes which respond to a wide range of irradiation conditions in different cell types and tissues. Functional analysis of the negatively modulated genes revealed a dominant signature of mitotic cell cycle regulation which appears both dose and time-dependent. This signature is prominent in cancer cells and highly proliferating tissues but it is strongly attenuated in non cancer cells.
  
  
  CONCLUSIONS
  The transcriptional response of mammalian cancer cells to irradiation is dominated by a mitotic cell cycle signature both dose and time-dependent. This core response, which is present in cancer cells and highly proliferating tissues such as skin, blood and lymph node, is weaker or absent in non-cancer cells and in liver and spleen. CDKN1A (cyclin-dependent kinase inhibitor 1A) appears as the most generally induced mammalian gene and its response (mostly dose- and time-independent) seems to go beyond the typical DNA damage response.
authors.affiliation: Laboratory of Functional Genomics and Proteomics of Model Systems, Department of Biology and Biotechnology Charles Darwin, University of Rome, La Sapienza.
authors.forename: Francesca
authors.initials: F
authors.lastname: Bufalieri
authors.forename: Valerio
authors.initials: V
authors.lastname: Licursi
authors.forename: Mattia
authors.initials: M
authors.lastname: D'Antonio
authors.forename: Tiziana
authors.initials: T
authors.lastname: Castrignanò
authors.forename: Roberto
authors.initials: R
authors.lastname: Amendola
authors.forename: Rodolfo
authors.initials: R
authors.lastname: Negri
mesh_terms: D000818:Animals; D002453:Cell Cycle / Q000528:radiation effects*; D018797:Cell Cycle Proteins / Q000378:metabolism*; D057225:Data Mining; D030541:Databases, Genetic; D030562:Databases, Protein; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D051379:Mice; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology*; D011829:Radiation Dosage; D014157:Transcription Factors / Q000378:metabolism*; D015533:Transcriptional Activation / Q000528:radiation effects*
chemical_list: D018797:Cell Cycle Proteins; D014157:Transcription Factors