title: Gene expression changes during repopulation in a head and neck cancer xenograft.
abstract: OBJECTIVE
  To investigate temporal changes in global gene expression and pathways involved in the response to irradiation during phases of growth inhibition, recovery and repopulation in a human head and neck squamous cell cancer (HNSCC) xenograft.
  
  
  METHODS
  Low passage head and neck squamous cancer cells (UT-14-SCC) were injected into the flanks of female nu/nu mice to generate xenografts. After tumors reached a size of 500 mm3, they were treated with either sham RT or 15Gy in one fraction. At different time points, days 0, 3, and 10 for controls and days 4, 7, 12, and 21 after irradiation, the tumors were harvested for global gene expression analysis and pathway analysis.
  
  
  RESULTS
  The tumors showed growth inhibition through days 4-7 and began the transition to regrowth around the day 12 time point. When comparing the pooled controls to each day of treatment, there were 22, 119, 125, and 25 differentially expressed genes on days 4, 7, 12, and 21 respectively using a p⩽0.01 and a 2-fold cut-off. Gene Ontology (GO), gene set enrichment analysis (GSEA) and sub-network enrichment analysis (SNEA) identified different biological processes, cell process pathways and expression targets to be active on each time point after irradiation. An important observation was that the molecular events on day 12 which represented the transition from growth inhibition to regrowth identified interferon and cytokine related genes and signaling pathways as the most prominent.
  
  
  CONCLUSIONS
  The findings in this study compliment research which has identified components of interferon-related signaling pathways to be involved in radioresistance. Further work will be required to understand the significance of these genes in both radioresistance and treatment response leading to new therapeutic strategies and prognostic tools.
authors.affiliation: Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, USA; Beaumont BioBank, William Beaumont Hospital, Royal OakUSA. Electronic address: george.wilson@beaumont.edu.
authors.forename: George D
authors.initials: GD
authors.lastname: Wilson
authors.affiliation: Beaumont BioBank, William Beaumont Hospital, Royal OakUSA.
authors.forename: Bryan J
authors.initials: BJ
authors.lastname: Thibodeau
authors.affiliation: Beaumont BioBank, William Beaumont Hospital, Royal OakUSA.
authors.forename: Laura E
authors.initials: LE
authors.lastname: Fortier
authors.affiliation: Beaumont BioBank, William Beaumont Hospital, Royal OakUSA.
authors.forename: Barbara L
authors.initials: BL
authors.lastname: Pruetz
authors.affiliation: Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, USA.
authors.forename: Sandra
authors.initials: S
authors.lastname: Galoforo
authors.affiliation: Beaumont BioBank, William Beaumont Hospital, Royal OakUSA; Department of Otolaryngology, William Beaumont Hospital, Royal Oak, USA.
authors.forename: Jan
authors.initials: J
authors.lastname: Akervall
authors.affiliation: Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, USA.
authors.forename: Brian
authors.initials: B
authors.lastname: Marples
authors.affiliation: Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, USA; Department of Radiation Oncology, Washington University School of Medicine, St. Louis, USA.
authors.forename: Jiayi
authors.initials: J
authors.lastname: Huang
mesh_terms: D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology / Q000532:radiotherapy; D002455:Cell Division; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression / Q000235:genetics*; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000473:pathology / Q000532:radiotherapy; D064593:Heterografts; D006801:Humans; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D011379:Prognosis; D012334:RNA, Neoplasm / Q000235:genetics; D011897:Random Allocation; D015398:Signal Transduction / Q000235:genetics; D000077195:Squamous Cell Carcinoma of Head and Neck; D014183:Transplantation, Heterologous
chemical_list: D012334:RNA, Neoplasm
keywords: Gene expression; Head and neck; Interferon; Repopulation