APC mutation and the initiation of colorectal cancer

结肠直肠癌是澳大利亚的一个主要健康问题。目前，它是最常见的癌症，大约每21个澳大利亚人中就有1个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。目前对晚期结直肠癌的治疗不是很有效。结直肠癌的死亡率很高，在澳大利亚仅次于肺癌，是癌症死亡的主要原因。结直肠癌的发展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。APC基因的突变与至少80%的结直肠肿瘤中肿瘤形成的早期阶段有关。我们的研究旨在了解APC的改变如何影响结肠细胞的行为和生长。我们已经开发了一种新的系统，其中正常的小鼠结肠可以在培养皿中维持和生长长达2周。APC基因和其他结肠癌基因的改变将被引入正常上皮细胞衬里，并将分析对器官培养中细胞生长和行为的影响。我们的假设是APC基因的变化影响细胞迁移、分裂和移动的方式。这项工作应该提高我们对肠道肿瘤发生过程中细胞变化的认识，旨在为结肠癌早期干预的新疗法的设计做出贡献。

Colorectal (or bowel) cancer is a major health problem in Australia. At present it is the most common cancer, 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 advanced colorectal cancer are not very effective. Mortality from colorectal cancer is high, being second only to lung cancer as the leading cause of cancer death in Australia. The development of colorectal cancer 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 gene known as APC are associated with the very early stages of tumour formation in at least 80% of colorectal tumours. Our research is aimed at understanding how alterations in APC influence the behaviour and growth of colonic cells. We have developed a novel system where normal mouse colon can be maintained and grown for up to 2 weeks in a Petri dish. Alterations in the APC gene and other colon cancer genes will be introduced into the normal epithelial cell lining and the effects on the growth and behaviour of the cells in organ culture will be analysed. Our hypothesis is that changes in the APC gene affects the way cells migrate, divide and move. This work should improve our knowledge of the cellular changes that occur during tumour initiation in the bowel and aims to contribute to the design of new therapies for early intervention in colon cancer.