文章：

散发性癌症条件小鼠模型

Conditional mouse models of sporadic cancer

原文发布日期：2002-04-01

DOI: 10.1038/nrc777

类型: Review Article

开放获取: 否

要点：

1. Sporadic cancer development is triggered by initiating mutations in a single cell, which result in tumour growth in a genetically wild-type environment that might actively contribute to tumour progression.
2. Tumour models that use conventional transgenic or knockout mice do not allow modelling of sporadic cancer, because the initiating mutation is present in all cells of a specific tissue or throughout the body. These cells include those that constitute the tumour microenvironment.
3. Various methods for conditional tumour-suppressor gene mutation and oncogene activation allow modelling of sporadic cancer in genetically engineered mice.
4. Recombinase-mediated conditional gene mutation can be used successfully to circumvent embryonic lethality or unwanted tumorigenesis in conventional tumour-suppressor gene knockouts.
5. Tumour growth and maintenance in mice with regulatable oncogene expression depends, in most cases, on continuous oncogene expression, supporting the validity of these factors as therapeutic targets.
6. Combining mouse models of sporadic cancer with various genome-wide screens for genetic alterations allows a comparison, on a molecular level, of mouse tumours with their human counterparts, and facilitates the discovery of new cancer genes and pathways that are involved in multistep tumorigenesis.
7. Mouse imaging systems that enable the non-invasive monitoring of tumour development will render conditional mouse models of sporadic cancer particularly useful for preclinical testing of therapeutic intervention or chemoprevention strategies.

要点翻译：

1. 散发性癌症的发生始于单个细胞中的起始突变，这些突变导致肿瘤在遗传学野生型环境中生长——这种环境可能 actively 促进肿瘤进展。
2. 使用传统转基因或敲除小鼠的肿瘤模型无法模拟散发性癌症，因为起始突变存在于特定组织的所有细胞或全身各处。这些细胞包括构成肿瘤微环境的细胞。
3. 多种条件性肿瘤抑制基因突变和癌基因激活方法使得在基因工程小鼠中模拟散发性癌症成为可能。
4. 重组酶介导的条件性基因突变可成功规避传统肿瘤抑制基因敲除中出现的胚胎致死性或非预期肿瘤发生。
5. 在大多数可调控癌基因表达的小鼠模型中，肿瘤的生长和维持依赖于癌基因的持续表达，这支持了这些因子作为治疗靶点的有效性。
6. 将散发性癌症小鼠模型与各种全基因组遗传改变筛查技术相结合，可在分子水平上对比小鼠肿瘤与人类肿瘤，有助于发现参与多步骤肿瘤发生的新癌症基因和通路。
7. 能够无创监测肿瘤发展的小鼠成像系统，将使条件性散发性癌症小鼠模型在治疗干预或化学预防策略的临床前测试中具有特殊价值。

英文摘要：

First-generation mouse tumour models, which used transgenic mice or conventional knockouts, are now being superseded by models that are based on conditional knockouts and mice that carry regulatable oncogenes. In these mice, somatic mutations can be induced in a tissue-specific and time-controlled fashion, which more faithfully mimics sporadic tumour formation. These second-generation models provide exciting new opportunities to gain insight into the contribution of known and unknown genes in the initiation, progression and treatment of cancer, and mimic human cancer better than ever before.

摘要翻译： 

第一代小鼠肿瘤模型使用转基因小鼠或传统敲除技术，现正被基于条件性敲除和携带可调控癌基因的小鼠模型所取代。在这些小鼠中，体细胞突变可在特定组织和特定时间被诱导，更真实地模拟了散发性肿瘤的形成。这些第二代模型为深入了解已知和未知基因在癌症发生、进展及治疗中的作用提供了令人兴奋的新机遇，比以往更真实地模拟了人类癌症。

原文链接：

Conditional mouse models of sporadic cancer