TUMOR SUPPRESSOR FUNCTION OF THE M6P/IGF2 RECEPTOR

描述：Jirtle博士的研究小组最近证明，甘露糖 6-磷酸/胰岛素样生长因子II受体（M6 P/IGF 2 r）基因是一个与胰岛素样生长因子II受体相关的基因。 人和大鼠肝细胞癌（HCC）中重要肿瘤抑制因子。 拟议的研究将集中在小鼠模型系统。 在目标1中， 将分析两种致癌物模型，以证明M6 P/IGF 2 r基因 存在病变。 目的2研究将评估M6 P/IGF 2 r的作用 在缺乏功能基因的HCC系中进行基因替换。 在目标3中，a 将评价过表达该基因的M6 P/IGF 2 r转基因的 对二乙基亚硝胺（DEN） 和邻苯二甲酸二[2-乙基-己基]酯（DEHP）。 最后，对于目标4研究， 将构建具有可诱导敲除的 M6 P/IGF 2 r基因在肿瘤发生模型中的评价。

DESCRIPTION: Dr. Jirtle's group has recently demonstrated that the mannose 6-phosphate/insulin-like growth factor II receptor (M6P/IGF2r) gene is an important tumor suppressor in human and rat hepatocellular carcinoma (HCC). The proposed studies will focus on mouse model systems. In Aim 1, HCCs from two carcinogen models will be analyzed to demonstrate that M6P/IGF2r gene lesions are present. Aim 2 studies will evaluate the effect of M6P/IGF2r gene replacement in an HCC line that lacks a functional gene. In Aim 3, a M6P/IGF2r transgenic that overexposes the gene will be evaluated for its sensitivity to liver carcinogenesis by two agents, diethylnitrosamine (DEN) and di[2-ethyl-hexyl]phthalate (DEHP). Finally, for Aim 4 studies, a transgenic mouse will be constructed with inducible knock-out of the M6P/IGF2r gene for evaluation in the carcinogenesis models.