TUMOR SUPPRESSOR FUNCTION OF THE M6P/IGF2 RECEPTOR

描述：Jirtle博士的团队最近证明了甘露糖 6-磷酸/胰岛素样生长因子II受体(M6P/IGF2r)基因是一种 人和大鼠肝细胞癌中重要的肿瘤抑制因子。 拟议的研究将集中在小鼠模型系统上。在目标1中，来自 将分析两种致癌模型以证明M6P/IGF2r基因 有损伤存在。目的2研究将评估M6P/IGF2r的效果 缺乏功能基因的肝癌细胞系中的基因替换。在目标3中，一个 过度暴露基因的M6P/IGF2r转基因将被评估其 二乙基亚硝胺(DEN)对肝癌的敏感性 和邻苯二甲酸二[2-乙基己酯](DEHP)。最后，对于AIM 4研究，一个 转基因小鼠将被构建成可诱导的敲除 评价M6P/IGF2r基因在致癌模型中的作用。

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.