Lee Ju-Seog, Chu In-Sun, Mikaelyan Arsen, Calvisi Diego F, Heo Jeonghoon, Reddy Janardan K, Thorgeirsson Snorri S
Laboratory of Experimental Carcinogenesis, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-4262, USA.
Nat Genet. 2004 Dec;36(12):1306-11. doi: 10.1038/ng1481. Epub 2004 Nov 21.
Genetically modified mice have been extensively used for analyzing the molecular events that occur during tumor development. In many, if not all, cases, however, it is uncertain to what extent the mouse models reproduce features observed in the corresponding human conditions. This is due largely to lack of precise methods for direct and comprehensive comparison at the molecular level of the mouse and human tumors. Here we use global gene expression patterns of 68 hepatocellular carcinomas (HCCs) from seven different mouse models and 91 human HCCs from predefined subclasses to obtain direct comparison of the molecular features of mouse and human HCCs. Gene expression patterns in HCCs from Myc, E2f1 and Myc E2f1 transgenic mice were most similar to those of the better survival group of human HCCs, whereas the expression patterns in HCCs from Myc Tgfa transgenic mice and in diethylnitrosamine-induced mouse HCCs were most similar to those of the poorer survival group of human HCCs. Gene expression patterns in HCCs from Acox1(-/-) mice and in ciprofibrate-induced HCCs were least similar to those observed in human HCCs. We conclude that our approach can effectively identify appropriate mouse models to study human cancers.
转基因小鼠已被广泛用于分析肿瘤发生过程中出现的分子事件。然而，在许多（即便不是所有）情况下，尚不确定小鼠模型在多大程度上重现了在相应人类病症中观察到的特征。这在很大程度上是由于缺乏在分子水平上对小鼠和人类肿瘤进行直接和全面比较的精确方法。在此，我们利用来自七种不同小鼠模型的68例肝细胞癌（HCC）以及来自预定义亚类的91例人类HCC的全局基因表达模式，以直接比较小鼠和人类HCC的分子特征。Myc、E2f1和Myc E2f1转基因小鼠的HCC中的基因表达模式与人类HCC中生存率较高组的最为相似，而Myc Tgfa转基因小鼠的HCC以及二乙基亚硝胺诱导的小鼠HCC中的表达模式与人类HCC中生存率较低组的最为相似。Acox1(-/-)小鼠的HCC以及环丙贝特诱导的HCC中的基因表达模式与在人类HCC中观察到的最不相似。我们得出结论，我们的方法能够有效地识别出用于研究人类癌症的合适小鼠模型。
