LH(BETA)T(AG) 视网膜母细胞瘤基因表达的区域和时间差异。
Regional and temporal differences in gene expression of LH(BETA)T(AG) retinoblastoma tumors.
机构信息
Bascom Palmer Eye Institute, Miami, FL 33101, USA.
出版信息
Invest Ophthalmol Vis Sci. 2011 Jul 23;52(8):5359-68. doi: 10.1167/iovs.10-6321.
PURPOSE
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.
目的
本研究通过微阵列评估了以下假说，即 LH(BETA)T(AG)视网膜母细胞瘤肿瘤在基因表达上表现出区域性和时间性的变化。
方法
处死 12、16 和 20 周龄的 LH(BETA)T(AG)小鼠（n=9）。从五个肿瘤区域（顶部、前外侧、中心、底部和后外侧）采集标本。将样本与基因微阵列杂交。对数据进行预处理和分析，根据 ANOVA 模型，P < 0.01，以及对数 2-倍变化>2.5 的基因被认为是差异表达的。通过通路分析工具，对差异表达基因进行分析，以与已知网络重叠。
结果
LH(BETA)T(AG)视网膜母细胞瘤肿瘤存在显著的时间（P < 10(-8))和区域差异。在 P < 0.01 和对数 2-倍变化>2.5 时，顶部有 190 个基因、前外侧有 84 个基因、后外侧有 126 个基因、中心有 56 个基因、底部有 134 个基因的基因表达发生显著变化。差异表达基因与已知网络重叠，显著参与细胞增殖和生长的调节、对氧水平和缺氧的反应、细胞过程的调节、细胞信号级联和血管生成。
结论
LH(BETA)T(AG)视网膜母细胞瘤模型存在显著的时间和区域变化。差异表达基因与可能在小鼠视网膜母细胞瘤发育中发挥关键作用的关键途径重叠。这些发现表明，参与小鼠视网膜母细胞瘤肿瘤生长和进展的机制，并确定了在功能水平上进行分析的途径，以确定人类视网膜母细胞瘤的意义。LH(BETA)T(AG)视网膜肿瘤的微阵列分析显示基因表达存在显著的区域和时间变化，包括缺氧反应和血管生成相关基因的失调。
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