Discovery and analysis of vertebrate intestinal development genes that may play a role in colon cancer

可能在结肠癌中发挥作用的脊椎动物肠道发育基因的发现和分析

• 批准号: nhmrc : 433614
• 负责人: A/Pr Joan Heath
• 金额: $ 25.11万
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2007
• 资助国家: 澳大利亚
• 起止时间: 2007-01-01 至 2008-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/discovery-analysis-vertebrate-colon-cancer/101449
• 关键词: Discovery; analysis; vertebrate; intestinal; development

Colorectal cancer (CRC) causes more cancer deaths in Australia than any other cancer. While early detection improves survival rate, nearly half of all CRC patients succumb to the disease within five years. In general, metastatic CRC is resistant to chemotherapy and radiotherapy and new therapies are required. An increased knowledge of the processes that contribute to the malignant state is likely to suggest new targets for treatment. CRC, like all cancer, is the result of genetic abnormalities (mutations) that are acquired over the course of a lifetime. Together the mutated genes produce changes in cell behaviour in processes such as growth, migration, angiogenesis (the ability to attract a blood supply) and cell death. All of these processes are active during normal development of a vertebrate organism, but are generally shutdown in the adult state, except in cancer. In this study we will analyse a group of genes that we have recently shown to be indispensable for normal intestinal development in zebrafish. Zebrafish are small tropical fish that are used frequently for genetic studies. They are very closely related to mammals and it has been shown that the genetic pathways that control the development of this animal are highly conserved in fish and mammals. Importantly, the genetic pathways that lead to cancer in humans are also strikingly similar in zebrafish. Our experiments will use mouse models to discover whether the zebrafish genes we have identified can lead to cancer when they are aberrantly expressed in the intestines of mice. Any genes that are found to contribute to the development of cancer in these models could become potential new targets for cancer therapy.

在澳大利亚，结直肠癌（CRC）导致的癌症死亡人数比任何其他癌症都多。虽然早期发现可以提高生存率，但近一半的CRC患者在五年内死于该疾病。一般来说，转移性CRC对化疗和放疗有抗性，需要新的治疗方法。对导致恶性状态的过程的更多了解可能会提出新的治疗目标。CRC与所有癌症一样，是一生中获得的遗传异常（突变）的结果。这些突变的基因一起在细胞生长、迁移、血管生成（吸引血液供应的能力）和细胞死亡等过程中产生细胞行为的变化。所有这些过程在脊椎动物有机体的正常发育期间都是活跃的，但在成年状态下通常关闭，癌症除外。在这项研究中，我们将分析一组基因，我们最近已经证明是必不可少的正常肠道发育的斑马鱼。斑马鱼是一种小型热带鱼，经常用于遗传研究。它们与哺乳动物非常密切相关，已经表明控制这种动物发育的遗传途径在鱼类和哺乳动物中高度保守。重要的是，导致人类癌症的遗传途径在斑马鱼中也惊人地相似。我们的实验将使用小鼠模型来发现我们已经鉴定的斑马鱼基因在小鼠肠道中异常表达时是否会导致癌症。在这些模型中发现的任何有助于癌症发展的基因都可能成为癌症治疗的潜在新靶点。