Genomic progression in mouse models for liver tumors.
Genomic progression in mouse models for liver tumors.
复制标题
肝肿瘤小鼠模型的基因组进展。
DOI：
10.1101/sqb.2005.70.058
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发表时间：
2005
期刊：
影响因子：
--
通讯作者：
Bishop,JM
中科院分区：
文献类型：
--
作者：
Tward,AD;Jones,KD;Yant,S;Kay,MA;Wang,R;Bishop,JM
人类肝癌的主要原因是感染了乙型和丙型肝炎病毒，但肿瘤的进展是由随后的扰动推动的，这些扰动导致原癌基因的功能增加或肿瘤抑制基因的功能丧失。在这些干扰中，常见的是原癌基因MET的过度表达。我们通过在近交系小鼠肝细胞中表达MET条件性转基因来模拟肝肿瘤的发病机制。对MET转基因的反应因其表达的大小和时间的不同而不同，但包括肝祖细胞的增殖，以及表现出与人类对应的表型和基因相似的良性和恶性肿瘤。结果揭示了MET是肝脏发育中的一个关键开关；戏剧性地展示了一个发育过程中不同的细胞间隔如何产生独特的肿瘤干细胞；描绘了肿瘤进展的规则；提供了证据，证明小鼠的实验性肿瘤是人类肿瘤的真实模型；并支持MET在人类肝脏肿瘤的发生中的作用。这些模型在阐明肿瘤发生机制和新疗法的临床前测试中应该是有用的。
The principal cause of human liver cancer is infection with hepatitis viruses B and C, but tumor progression is fueled by ensuingperturbations that confer gain of function on proto-oncogenes or loss of function on tumor suppressor genes. Frequentamong these perturbations is overexpression of the proto-oncogene MET. We have modeled the pathogenesis of liver tumorsby expressing conditional transgenes of MET in the hepatocytes of inbred mice. The response to the MET transgene variedwith both the magnitude and timing of its expression but included hyperplasia of hepatic progenitor cells, as well as benignand malignant tumors that display both phenotypic and genotypic resemblances to human counterparts. The results revealMET to be a crucial switch in the development of the liver; dramatize how different cellular compartments within a developmentallineage can give rise to distinctive tumor stem cells; delineate rules of tumor progression; provide evidence that theexperimental tumors in mice are authentic models for human tumors; and support a role for MET in the genesis of humanliver tumors. The models should be useful in elucidating the mechanisms of tumorigenesis and in the preclinical testing ofnew therapeutics.