Using a novel gut culture system to analyse the influence of genes mutated in colon cancer on epithelial cell growth

结肠直肠癌是澳大利亚的一个主要健康问题。大约每21名澳大利亚人中就有1人会在一生中患上这种疾病。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。目前对结直肠癌的治疗不是很有效，患有这种疾病的患者的中位生存期很差，为7- 12个月。结直肠癌的发展是复杂的，受遗传和环境因素的影响。结直肠癌的发展经历了许多不同的病理阶段。这被认为是基因突变的逐步获得的结果，通常确保细胞生长和细胞死亡之间的平衡。许多基因（称为APC，K-ras，p53，SMAD 2，SMAD 4）的突变通常在结直肠肿瘤中发现。这项研究旨在了解结肠癌中改变的基因如何影响正常肠道细胞的生长。我们已经开发了一个系统，在这个系统中，正常的小鼠肠道可以保持完整并生长。含有在结肠癌中发现的改变的基因将被引入正常的肠道上皮细胞，并分析对这些细胞生长和行为的影响。这将提高我们对这些改变的基因如何促进结肠癌发展的认识。

Colorectal (or bowel) cancer is a major health problem in Australia. Approximately 1 in 21 Australians will develop the disease in his-her lifetime. The risk of bowel cancer increases with age, with the risk rising progressively and sharply from the age of 50. Current therapies for colorectal cancer are not very effective and the median survival for patients with this disease is poor at 7- 12 months. The development of colorectal cancer is complex and is affected by both genetic and environmental factors. Colorectal cancer progresses through a number of distinct pathological stages. This is thought to be the result of the progressive aquisition of mutations in genes that normally ensure a balance between cell growth and cell death. Mutations in a number of genes (known as APC, K-ras, p53, SMAD2, SMAD4) are commonly found in colorectal tumours. This research is aimed at understanding how genes which are altered in colon cancer influence the growth of cells in normal intestine. We have developed a system where normal mouse gut can be maintained and grown intact. Genes containing the alterations found in colon cancer will be introduced into the normal gut epithelial cells and the effects on the growth and behaviour of these cells analysed. This should improve our knowledge of how these altered genes contribute to the development of colon cancer.