Investigation Of Cancer Predisposition In Heterozygous Carriers Of The ATM
Funder
National Health and Medical Research Council
Funding Amount
$822,750.00
Summary
Individuals with the human genetic disorder ataxia-telangiectasia are prone to cancer development and so also are their parents and relatives (carriers) who have one defective copy of the gene. This is a multisystem disease that is also characterized by neurodegeneration, immunodeficiency, infertility and extreme sensitivity to radiation. This project is designed to generate a mouse model of this disease to investigate cancer susceptibility in carriers of the defective gene. The specific mutatio ....Individuals with the human genetic disorder ataxia-telangiectasia are prone to cancer development and so also are their parents and relatives (carriers) who have one defective copy of the gene. This is a multisystem disease that is also characterized by neurodegeneration, immunodeficiency, infertility and extreme sensitivity to radiation. This project is designed to generate a mouse model of this disease to investigate cancer susceptibility in carriers of the defective gene. The specific mutation to be introduced into the mouse has been described in a patient with breast cancer and it has been shown to interfere with the normal function of the ATM protein. The mouse model is expected to reflect closely the human disease and will provide the opportunity to monitor heterozygous carriers for the development of cancer. This model is expected to confirm the observations in humans and provide a resource to understand susceptibility to develop cancer. The model will also address the issue of exposure to low dose radiation and risk of developing cancer.Read moreRead less
Using The A33 Antigen Gene Locus To Generate Novel Mouse Models Of Colon Cancer
Funder
National Health and Medical Research Council
Funding Amount
$376,320.00
Summary
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 ....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.Read moreRead less