Analysis of the effects of cell growth and cell death regulation on tumor development using tumor mice models

其中组成型活性Ras在肝脏中特异性表达的转基因小鼠（RasV 12-肝小鼠）发生肝细胞癌（HCC）。我们发现Ras转基因小鼠在缺乏Tob蛋白的情况下更频繁地发生HCC。此外，在Tob蛋白不存在的情况下，肿瘤的大小明显更大。这些数据表明，Tob负责抑制HCC的发展和增殖。我们还研究了RasV 12-肝小鼠和缺乏Tob的RasV 12-肝小鼠之间的基因表达差异。我们观察了几个参与细胞生长和死亡调控的基因的表达变化。这些基因的表达变化在十多个小鼠样本中也被类似地检测到，表明这些基因对HCC的发展至关重要。

Transgenic mice in which constitutively active Ras is specifically expressing in the liver (RasV12-liver mice) develop hepatocellular carcinoma (HCC). We found that the Ras-transgenic mice much more frequently develop HCC in the absence of Tob protein. Furthermore, the size of the tumors was obviously larger in the absence of Tob protein. These data suggest that Tob is responsible for suppressing HCC development and proliferation. We also examined the difference of gene expression between RasV12-liver mice and RasV12-liver mice lacking Tob. We observed the expression change in several genes involved in cell growth and death regulation. The expression change of those genes was similarly detected in more than ten mice samples, indicating that those genes are critically responsible for HCC development.