title: Regional and temporal differences in gene expression of LH(BETA)T(AG) retinoblastoma tumors.
abstract: OBJECTIVE
  The purpose of this study was to evaluate by microarray the hypothesis that LH(BETA)T(AG) retinoblastoma tumors exhibit regional and temporal variations in gene expression.
  
  
  METHODS
  LH(BETA)T(AG) mice aged 12, 16, and 20 weeks were euthanatized (n = 9). Specimens were taken from five tumor areas (apex, anterior lateral, center, base, and posterior lateral). Samples were hybridized to gene microarrays. The data were preprocessed and analyzed, and genes with a P < 0.01, according to the ANOVA models, and a log(2)-fold change >2.5 were considered to be differentially expressed. Differentially expressed genes were analyzed for overlap with known networks by using pathway analysis tools.
  
  
  RESULTS
  There were significant temporal (P < 10(-8)) and regional differences in gene expression for LH(BETA)T(AG) retinoblastoma tumors. At P < 0.01 and log(2)-fold change >2.5, there were significant changes in gene expression of 190 genes apically, 84 genes anterolaterally, 126 genes posteriorly, 56 genes centrally, and 134 genes at the base. Differentially expressed genes overlapped with known networks, with significant involvement in regulation of cellular proliferation and growth, response to oxygen levels and hypoxia, regulation of cellular processes, cellular signaling cascades, and angiogenesis.
  
  
  CONCLUSIONS
  There are significant temporal and regional variations in the LH(BETA)T(AG) retinoblastoma model. Differentially expressed genes overlap with key pathways that may play pivotal roles in murine retinoblastoma development. These findings suggest the mechanisms involved in tumor growth and progression in murine retinoblastoma tumors and identify pathways for analysis at a functional level, to determine significance in human retinoblastoma. Microarray analysis of LH(BETA)T(AG) retinal tumors showed significant regional and temporal variations in gene expression, including dysregulation of genes involved in hypoxic responses and angiogenesis.
authors.affiliation: Bascom Palmer Eye Institute, Miami, FL 33101, USA.
authors.forename: Samuel K
authors.initials: SK
authors.lastname: Houston
authors.forename: Yolanda
authors.initials: Y
authors.lastname: Pina
authors.forename: Jennifer
authors.initials: J
authors.lastname: Clarke
authors.forename: Tulay
authors.initials: T
authors.lastname: Koru-Sengul
authors.forename: William K
authors.initials: WK
authors.lastname: Scott
authors.forename: Lubov
authors.initials: L
authors.lastname: Nathanson
authors.forename: Amy C
authors.initials: AC
authors.lastname: Schefler
authors.forename: Timothy G
authors.initials: TG
authors.lastname: Murray
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D004195:Disease Models, Animal; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D052138:Genes, Neoplasm / Q000235:genetics*; D000860:Hypoxia / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D009363:Neoplasm Proteins / Q000235:genetics*; D009389:Neovascularization, Pathologic / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D010100:Oxygen / Q000378:metabolism; D019572:Retinal Neoplasms / Q000235:genetics*; D012175:Retinoblastoma / Q000235:genetics*
chemical_list: D009363:Neoplasm Proteins; D010100:Oxygen