TY - JOUR
T1 - Regional and temporal differences in gene expression of LH BETAT AG retinoblastoma tumors
AU - Houston, Samuel K.
AU - Pina, Yolanda
AU - Clarke, Jennifer
AU - Koru-Sengul, Tulay
AU - Scott, William K.
AU - Nathanson, Lubov
AU - Schefler, Amy C.
AU - Murray, Timothy G.
PY - 2011/7
Y1 - 2011/7
N2 - Purpose. The purpose of this study was to evaluate by microarray the hypothesis that LH BETAT AG retinoblastoma tumors exhibit regional and temporal variations in gene expression. Methods. LH BETAT 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 log2-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 BETAT AG retinoblastoma tumors. At P < 0.01 and log2-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 BETAT 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 BETAT AG retinal tumors showed significant regional and temporal variations in gene expression, including dysregulation of genes involved in hypoxic responses and angiogenesis.
AB - Purpose. The purpose of this study was to evaluate by microarray the hypothesis that LH BETAT AG retinoblastoma tumors exhibit regional and temporal variations in gene expression. Methods. LH BETAT 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 log2-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 BETAT AG retinoblastoma tumors. At P < 0.01 and log2-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 BETAT 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 BETAT AG retinal tumors showed significant regional and temporal variations in gene expression, including dysregulation of genes involved in hypoxic responses and angiogenesis.
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U2 - 10.1167/iovs.10-6321
DO - 10.1167/iovs.10-6321
M3 - Article
C2 - 21571674
AN - SCOPUS:80052012074
VL - 52
SP - 5359
EP - 5368
JO - Investigative Ophthalmology and Visual Science
JF - Investigative Ophthalmology and Visual Science
SN - 0146-0404
IS - 8
ER -