Using the A33 antigen gene locus to generate novel mouse models of colon cancer

使用 A33 抗原基因位点生成新型结肠癌小鼠模型

• 批准号: nhmrc : 191505
• 负责人: A/Pr Joan Heath
• 金额: $ 25.09万
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2002
• 资助国家: 澳大利亚
• 起止时间: 2002-01-01 至 2004-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/using-a33-antigen-colon-cancer/78036
• 关键词: Using; A33; antigen; gene; locus

Colorectal (or bowel) cancer is a major health problem in Australia. It is the most common cancer reported to Australian cancer registries and was responsible for 14% of cancer deaths in 1990, the latest year for which national figures are available. Only lung cancer, which caused 20% of cancer deaths was a more common cause of cancer death. Approximately 1 in 21 Australians will develop colorectal cancer during his-her lifetime. The risk of colorectal cancer increases with age, with risk rising progressively and sharply from age 50 onwards. Like all cancers, colorectal cancer results from the progressive acquisition of mutations in genes that normally ensure a balance between cell growth and cell death. Mutations which predispose individuals to colorectal cancer accumulate in the epithelial cells that provide the lining to the bowel. The progression of colorectal cancer proceeds through a number of distinct anatomical stages which can be easily recognised by pathologists. Mutations in a number of genes (known as APC, beta-catenin, Kirsten-ras, p53, SMAD2, SMAD4) are commonly found in colorectal tumours. Moreover, some of the mutations are highly associated with distinct stages of colon tumour development. As yet, however, we have no real insights into how these mutations cooperate with each other to produce full-blown (malignant) colorectal cancer. In our proposal, we are aiming to establish colorectal cancer in mice. Our approach will be to progressively introduce mutant genes into intestinal epithelial cells (singly and in combination) and study how they cooperate with each other to produce benign, and ultimately, malignant tumours in the intestines of mice. This will help us to understand which mutant genes are required for each stage in tumour development and may provide more rational approaches to bowel cancer screening and treatment.

结肠直肠癌是澳大利亚的一个主要健康问题。它是澳大利亚癌症登记处报告的最常见的癌症，在1990年占癌症死亡人数的14%，这是最近一年的国家数据。只有肺癌，造成20%的癌症死亡，是癌症死亡的一个更常见的原因。大约每21名澳大利亚人中就有1人会在一生中患上结直肠癌。结直肠癌的风险随着年龄的增长而增加，从50岁开始，风险逐渐急剧上升。像所有癌症一样，结直肠癌是由基因突变的渐进性获得引起的，这些突变通常确保细胞生长和细胞死亡之间的平衡。使个体易患结直肠癌的突变在提供肠衬里的上皮细胞中积累。结直肠癌的进展通过许多不同的解剖学阶段进行，这些阶段可以很容易地被病理学家识别。许多基因（称为APC，β-连环蛋白，Kirsten-ras，p53，SMAD 2，SMAD 4）的突变通常在结直肠肿瘤中发现。此外，一些突变与结肠肿瘤发展的不同阶段高度相关。然而，到目前为止，我们还没有真实的见解，这些突变如何相互合作，以产生全面的（恶性）结直肠癌。在我们的提案中，我们的目标是在小鼠中建立结直肠癌。我们的方法将是逐步将突变基因引入肠上皮细胞（单独和组合），并研究它们如何相互合作，在小鼠肠道中产生良性肿瘤，并最终产生恶性肿瘤。这将有助于我们了解肿瘤发展的每个阶段都需要哪些突变基因，并可能为肠癌筛查和治疗提供更合理的方法。