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

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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.