Using the Drosophila fly intestine to investigate Wnt targets in vivo

使用果蝇肠道研究体内 Wnt 靶标

• 批准号: G1000078/1
• 负责人: Owen James Sansom
• 金额: $ 44.66万
• 依托单位: University of Glasgow
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2010
• 资助国家: 英国
• 起止时间: 2010 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=G1000078%2F1
• 关键词: Using; Drosophila; fly; intestine; investigate

Colorectal Cancer is the third most common cancer and the second most common cause of cancer death. The Apc (Adenomatous Polyposis Coli) gene is mutated in nearly 80% of cancers but rarely in other cancers. Moreover Apc mutation appears to occur at the very earliest stages of colorectal cancer. Therefore it is vital for us to understand what the impact Apc mutation has upon normal cells from the colon. This has proved particularly difficult to study in cells taken from humans and mice as normal colon cells do not surivive well in the laboratory on plastic dishes. Also colorectal cancer cells taken from patients have already lost the Apc gene so making it difficult to elucidate what Apc does in normal cells to stop cancer. Therefore numerous studies have been performed in mice where the Apc gene is removed by genetic technology in the adult intestine/colon and then the changes that occur are monitored. In this proposal, we aim to assess whether removing Apc from the Drosophila fruitfly intestine would be an equally good model for studying the changes that occur. Specifically we are interested in the signalling pathway called Wnt which goes up following Apc loss and is very similar between flies, mice and humans. Thus our aim is to knockdown the proteins that go up following Apc loss and see if they can stop cancer. If we can validate the fly as test system for these studies, this will reduce the number of mouse experiments dramatically we need to perform. Moreover, this work may provide novel therapeutic targets for the treatment of colorectal cancer,

结直肠癌是第三大常见癌症，也是导致癌症死亡的第二大常见原因。APC(腺瘤性息肉病结肠)基因在近80%的癌症中发生突变，但在其他癌症中很少发生。此外，APC突变似乎发生在结直肠癌的最早期阶段。因此，了解APC突变对结肠正常细胞的影响是至关重要的。事实证明，在从人类和老鼠身上提取的细胞中研究这一点尤其困难，因为正常的结肠细胞在实验室的塑料培养皿中不能很好地存活。此外，从患者身上提取的结直肠癌细胞已经丢失了APC基因，因此很难阐明APC在正常细胞中起到什么作用来阻止癌症。因此，许多研究已经在小鼠身上进行，通过基因技术在成年肠道/结肠中移除APC基因，然后监测所发生的变化。在这项建议中，我们的目标是评估从果蝇肠道中移除APC是否也是研究所发生的变化的一个同样好的模型。具体来说，我们对称为Wnt的信号通路感兴趣，它在APC丢失后上升，与苍蝇、小鼠和人类非常相似。因此，我们的目标是敲除在APC丢失后上升的蛋白质，看看它们是否能阻止癌症。如果我们能够验证苍蝇作为这些研究的测试系统，这将大大减少我们需要进行的小鼠实验的数量。此外，本工作可能为结直肠癌的治疗提供新的治疗靶点。