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

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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.