Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, California; Liver Center, University of California, San Francisco, California.
Institute of Pathology, University of Greifswald, Greifswald, Germany.
Am J Pathol. 2014 Apr;184(4):912-923. doi: 10.1016/j.ajpath.2013.12.002. Epub 2014 Jan 28.
Primary liver cancers, including hepatocellular carcinoma and intrahepatic cholangiocarcinoma, are leading causes of cancer-related death worldwide. Recent large-scale genomic approaches have identified a wide number of genes whose deregulation is associated with hepatocellular carcinoma and intrahepatic cholangiocarcinoma development. Murine models are critical tools to determine the oncogenic potential of these genes. Conventionally, transgenic or knockout mouse models are used for this purpose. However, several limitations apply to the latter models. Herein, we review a novel approach for stable gene expression in mouse hepatocytes by hydrodynamic injection in combination with Sleeping Beauty-mediated somatic integration. This method represents a flexible, reliable, and cost-effective tool to generate preclinical murine models for liver cancer research. Furthermore, it can be used as an in vivo transfection method to study biochemical cross talks among multiple pathways along hepatocarcinogenesis and to test the therapeutic potential of drugs against liver cancer.
原发性肝癌包括肝细胞癌和肝内胆管细胞癌，是全球癌症相关死亡的主要原因。最近的大规模基因组研究方法已经确定了许多基因，这些基因的失调与肝细胞癌和肝内胆管细胞癌的发展有关。小鼠模型是确定这些基因致癌潜力的关键工具。传统上，使用转基因或基因敲除小鼠模型来实现这一目的。然而，后者模型存在一些局限性。在这里，我们综述了一种通过水力注射与 Sleeping Beauty 介导的体基因整合相结合在小鼠肝细胞中稳定表达基因的新方法。该方法代表了一种灵活、可靠且具有成本效益的工具，可用于生成用于肝癌研究的临床前小鼠模型。此外，它可以用作体内转染方法，以研究肝癌发生过程中多个途径之间的生化相互作用，并测试针对肝癌的药物的治疗潜力。
