Insights into gene expression changes impacting B-cell transformation: Cross-species microarray analysis of bovine leukemia virus tax-responsive genes in ovine B cells
Insights into gene expression changes impacting B-cell transformation: Cross-species microarray analysis of bovine leukemia virus tax-responsive genes in ovine B cells
复制标题
DOI：
10.1128/jvi.80.4.1922-1938.2006
复制
发表时间：
2006-02-01
影响因子：
5.4
通讯作者：
Van den Broeke, A
中科院分区：
文献类型：
--
作者：
Klener, P;Szynal, M;Van den Broeke, A
白血病的大动物模型有可能帮助理解有助于肿瘤发生的网络。牛白血病病毒（BLV）是一种与人类T细胞白血病病毒1型（HTLV-1）相关的复杂逆转录病毒，牛和绵羊感染BLV与B细胞白血病的发生有关。尽管牛的自然疾病的特征是肿瘤发病率低，但绵羊的实验性感染导致大多数感染动物出现明显的白血病，为研究与BLV和HTLV-1相关的发病机制提供了模型。Tax（BVL）是一种主要的癌蛋白，启动一系列导致恶性肿瘤的事件，尽管其转化的基础还不完全清楚。我们已经采取了跨物种的绵羊到人的微阵列方法，以确定税（BVL）的反应性转录变化，在两组培养的绵羊B细胞后，逆转录病毒载体介导的交付税（BLV）。使用包含10，336个人类基因/表达序列标签的cDNA点样微阵列，我们鉴定了一组差异表达基因，包括与凋亡、DNA转录和修复相关的基因;原癌基因;细胞周期调节因子;转录因子;小Rho GTP酶/GTP酶结合蛋白;以及先前报道的Tax（HTLV-1）响应基因。有趣的是，已知与人类肿瘤相关的基因，特别是B细胞恶性肿瘤，被广泛代表。有些是新奇的或意想不到的。结果表明，税收（BLV）解除管制的相互关联的途径，而不是一个单一的B谱系特定的监管过程的广泛网络。虽然跨物种的方法不允许基因表达模式的全面分析，但它们可以为参与B细胞转化的基因的功能作用提供初步线索，并确定在动物模型中使用其他方法未确定的分子靶点。
Large-animal models for leukemia have the potential to aid in the understanding of networks that contribute to oncogenesis. Infection of cattle and sheep with bovine leukemia virus (BLV), a complex retrovirus related to human T-cell leukemia virus type 1 (HTLV-1), is associated with the development of B-cell leukemia. Whereas the natural disease in cattle is characterized by a low tumor incidence, experimental infection of sheep leads to overt leukemia in the majority of infected animals, providing a model for studying the pathogenesis associated with BLV and HTLV-1. Tax(BVL) the major oncoprotein, initiates a cascade of events leading toward malignancy, although the basis of transformation is not fully understood. We have taken a cross-species ovine-to-human microarray approach to identify Tax(BVL)-responsive transcriptional changes in two sets of cultured ovine B cells following retroviral vector-mediated delivery of Tax(BLV). Using cDNA-spotted microarrays comprising 10,336 human genes/expressed sequence tags, we identified a cohort of differentially expressed genes, including genes related to apoptosis, DNA transcription, and repair; proto-oncogenes; cell cycle regulators; transcription factors; small Rho GTPases/GTPase-binding proteins; and previously reported Tax(HTLV-1)-responsive genes. Interestingly, genes known to be associated with human neoplasia, especially B-cell malignancies, were extensively represented. Others were novel or unexpected. The results suggest that Tax(BLV) deregulates a broad network of interrelated pathways rather than a single B-lineage-specific regulatory process. Although cross-species approaches do not permit a comprehensive analysis of gene expression patterns, they can provide initial clues for the functional roles of genes that participate in B-cell transformation and pinpoint molecular targets not identified using other methods in animal models.