Genetic induction of tumorigenesis in Swine
Genetic induction of tumorigenesis in Swine
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DOI：
10.1038/sj.onc.1209892
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发表时间：
2007-02-01
期刊：
影响因子：
8
通讯作者：
Counter, C. M.
中科院分区：
文献类型：
--
作者：
Adam, S. J.;Rund, L. A.;Counter, C. M.
由于缺乏遗传可塑性的大型动物模型，许多实验疗法从基础癌症研究向临床癌症研究的过渡受到阻碍。为此，我们通过基因工程改造原代猪细胞，使其通过表达已知干扰人类癌症中常见的破坏途径的蛋白质而致瘤。与人类细胞类似，这些猪细胞对转化具有很强的抵抗力，需要多种遗传变化。此外，转化的猪细胞在返回到同基因宿主动物时产生肿瘤。现在快速和可重复地遗传诱导肿瘤的能力在许多方面类似于人类的大型哺乳动物中与临床治疗的肿瘤相似，这将为依赖于产生大肿瘤的临床前研究提供稳健的癌症模型。
The transition from basic to clinical cancer research for a number of experimental therapeutics is hampered by the lack of a genetically malleable, large animal model. To this end, we genetically engineered primary porcine cells to be tumorigenic by expression of proteins known to perturb pathways commonly corrupted in human cancer. Akin to human cells, these porcine cells were quite resistant to transformation, requiring multiple genetic changes. Moreover, the transformed porcine cells produced tumors when returned to the isogenic host animal. The ability to now rapidly and reproducibly genetically induce tumors of sizes similar to those treated clinically in a large mammal similar to humans in many respects will provide a robust cancer model for preclinical studies dependant on generating large tumors.