Cross-species oncogenomics using zebrafish models of cancer.
Cross-species oncogenomics using zebrafish models of cancer.
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DOI：
10.1016/j.gde.2015.04.006
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发表时间：
2015-02
影响因子：
4
通讯作者：
White RM
中科院分区：
文献类型：
--
作者：
White RM
近年来，斑马鱼已成为癌症生物学的重要模型。这种鱼最初是在20世纪50年代开发的，作为毒性测试的模型[2]，但在20世纪60年代至90年代，它成为发育遗传学的发电站[4]。认识到斑马鱼适合基于ENU的正向遗传筛选，导致最终大规模努力创建突变斑马鱼的大池，每个突变斑马鱼具有与个体遗传突变相关的特定表型[5，6]。最初，这些表型中的许多表型围绕特定的细胞类型或组织[7]，但人们很早就认识到斑马鱼对肿瘤特别敏感[8]。这些肿瘤中的许多是自发发生的或在p53缺陷背景下发生的[9]，但可以通过DMBA等诱变剂迅速加速[10]。快速有效的转基因技术的出现彻底改变了斑马鱼在癌症研究中的应用[11，12]。因为每对鱼交配迅速，每天产生数百个胚胎，很明显，这是一个适合大规模，无偏见的癌症表型方法的模型。在其最直接的迭代中，细胞类型特异性启动子下的显性作用癌基因可用于产生各种肿瘤，如黑素瘤，如图1所示[1，3，13]。最近，使用各种过表达和敲除技术开发了越来越复杂的癌症模型。表1中显示了一系列可用的斑马鱼癌症模型。
In recent years, the zebrafish has emerged as an important model in cancer biology. The fish was originally developed in the 1950s as a model for toxicity testing [2] but during the 1960s–1990s it emerged as a powerhouse of developmental genetics [4]. The realization that the zebrafish was amenable to ENU-based, forward genetic screens led to the eventual largescale effort to create large pools of mutant zebrafish each with a specific phenotype linked to an individual genetic mutation [5, 6]. Initially, many of these phenotypes centered around specific cell types or tissues [7] but it was recognized early on that the zebrafish was especially sensitive to neoplasia [8]. Many of these tumors developed spontaneously or in p53 deficient backgrounds [9] but could be rapidly accelerated by mutagens such as DMBA [10].The emergence of rapid and efficient transgenic technologies revolutionized the use of zebrafish in cancer research [11, 12]. Because each pair of fish mates rapidly and produce hundreds of embryos per day, it was clear that it was a model amenable to large scale, unbiased approaches to cancer phenotypes. In its most straightforward iteration, dominant acting oncogenes under cell-type specific promoters can be used to produce a wide variety of tumors such as melanoma, as shown in Figure 1 [1, 3, 13]. More recently, increasingly complex models of cancer have been developed using a variety of overexpression and knockout technologies. A range of the available cancer models in zebrafish is shown in Table 1.