In Vivo Role Of LMO4 And Isolation Of An LMO4-containing Proteosome In Breast Cancer
Funder
National Health and Medical Research Council
Funding Amount
$455,250.00
Summary
Breast cancer is the most common cancer to affect women, with one in 10 developing the disease. Although treatment of breast cancer has substantially improved over the last few years, 25% of women diagnosed with this cancer will die from the disease. A major objective of cancer research is the identification of genes involved in tumour development and definition of their precise role in both normal and cancer cells. The design of effective therapeutic inhibitors of cancer requires an understandi ....Breast cancer is the most common cancer to affect women, with one in 10 developing the disease. Although treatment of breast cancer has substantially improved over the last few years, 25% of women diagnosed with this cancer will die from the disease. A major objective of cancer research is the identification of genes involved in tumour development and definition of their precise role in both normal and cancer cells. The design of effective therapeutic inhibitors of cancer requires an understanding of the basic molecular and cellular biology behind the genetic changes thought to contribute to cancer. The focus of our research is to understand normal cellular mechanisms that drive growth and differentiation of breast tissue, and those changes that lead to breast cancer. Nuclear regulatory proteins have been implicated in many different types of cancers and leukaemias. We aim to identify the key regulators in breast tissue, characterising both their structural properties and biological roles, with the ultimate view of understanding how they divert a normal cell to a cancerous cell. This proposal centres on the characterisation of a specific regulatory molecule which we recently demonstrated to be overexpressed in 56% of human primary breast cancers and in 38% of pre-invasive ductal carcinoma in situ. These studies will include defining its normal biologic function and identification of the proteins that this regulator associates with in breast cancer cells.Read moreRead less
Convergence Of Activated C-myb And Wnt Pathways In Colon Cancer
Funder
National Health and Medical Research Council
Funding Amount
$256,320.00
Summary
c-myb is essential for the normal biology of the blood system and the colon. It is involved in regulating the balance between the production of new cells and their timely removal once they have completed their assigned tasks. Another group of factors that make up theWnt pathway also contribute to the normal biology of the colon in man and mouse. Defects that lead to too much c-myb and ineffective control of the Wnt pathway appear to work together to increase the risk and severity of colon cancer ....c-myb is essential for the normal biology of the blood system and the colon. It is involved in regulating the balance between the production of new cells and their timely removal once they have completed their assigned tasks. Another group of factors that make up theWnt pathway also contribute to the normal biology of the colon in man and mouse. Defects that lead to too much c-myb and ineffective control of the Wnt pathway appear to work together to increase the risk and severity of colon cancer. This project is designed to specifically test this observation in animals. In addition it examines in fine detail how c-myb levels increase in colon cancer and how it combines with the Wnt pathway to regulate other genes in colon cancer.Read moreRead less
Transgenic Expression Of The EWS-WT1 Fusion Protein,inducing The Development Of Tumour That Replicates The Human Disease
Funder
National Health and Medical Research Council
Funding Amount
$112,976.00
Summary
A genetic translocation encoding the EWS-WT1 fusion protein is found desmoplastic small round cell tumours. Our aim is to examine the effect of this protein in inducing tumour growth in tissue cell lines. A virus will then be used to introduce the genetic translocation into mice to examine the effect of this protein on tumour growth in a mammal, thereby serving as a 'solid tumour model' to try and identify therapeutic targets.
Investigating Tumour Biology Using Regulated RNAi In Cells And Mice
Funder
National Health and Medical Research Council
Funding Amount
$305,915.00
Summary
Inhibiting gene expression using the recently discovered process known as RNA interference (RNAi) can be used as an experimental tool to analyse specific genes, in cells and genetically engineered animal models of human disease. I propose to use RNAi to mimic human cancer gene mutations in mouse cancer models, and aim to discover novel tumour suppressor genes. A further aim is to validate potential drug targets in cancer by using RNAi to inhibit specific genes in established mouse tumours.
Interaction Of Mc1r With The PRb And P53 Pathways In UVR-induced Melanoma Development
Funder
National Health and Medical Research Council
Funding Amount
$553,479.00
Summary
This project will shed light onto fundamental processes causing UV-induced melanoma (MM). Innate differences between individuals, independent of pigmentation, influence MM development. We will study the mechanisms of UVR-induced MM development in mice carrying gene mutations (Cdk4, Arf, Mc1r) that underpin human MM susceptibility. Knowledge of the sensitivity of an one's MCs to UV could be critical for targeting susceptible groups for health education campaigns and more intense screening.
Genetic Dissection Of The Gp130 Signalling Network; Implications In The Initiation Of Gastric Cancer
Funder
National Health and Medical Research Council
Funding Amount
$447,500.00
Summary
Stomach cancer is a major health problem in the world. It is the second most common cancer and the second leading cause of death from cancer, behind lung cancer. In fact, approximately 10% of all new reported cancer cases world-wide are stomach cancer. The risk of stomach cancer increases with age, with risk rising progressively and peaking at about 60 years of age. Men are affected twice as often as women Like all cancers, stomach cancer results from the progressive acquisition of mutations in ....Stomach cancer is a major health problem in the world. It is the second most common cancer and the second leading cause of death from cancer, behind lung cancer. In fact, approximately 10% of all new reported cancer cases world-wide are stomach cancer. The risk of stomach cancer increases with age, with risk rising progressively and peaking at about 60 years of age. Men are affected twice as often as women Like all cancers, stomach 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 stomach cancer accumulate in the epithelial cells that provide the lining to the stomach. The progression of stomach cancer proceeds through a number of distinct anatomical stages which can be easily recognised by pathologists. Mutations in a number of genes (known as Kirsten-ras, p53) are commonly found in stomach tumours. Moreover, some of the mutations are highly associated with distinct stages of tumour development. As yet, however, we have no real insights into how these mutations cooperate with each other to produce full-blown (malignant) stomach cancer. In our proposal, we are aiming to establish stomach cancer in mice. Our approach will be to use an existing animal model which is predisposed to stomach cancer. We will progressively introduce mutant genes into stomach epithelial cells and study how they cooperate with each other to produce benign, and ultimately, malignant tumours in the stomach 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 stomac cancer screening and treatment.Read moreRead less
Interactions Between Hedgehog And Ras Signaling In Lung Adenocarcinoma
Funder
National Health and Medical Research Council
Funding Amount
$295,983.00
Summary
Lung cancer is a common and lethal disease in our community. In this project, we explore how signaling pathways that regulate the development of the lung in embryos contribute to the initation and progression of lung cancer. To do this, we use a mouse model of lung cancer in which we can activate embryonic signaling pathways in adult mice to study there effect on the disease. Understanding these pathways will help us to better treat and prevent lung cancer in humans.
BIOLOGICAL STUDIES OF A NEW RECURRENT FUSION GENE FOUND IN T-CELL LEUKAEMIA
Funder
National Health and Medical Research Council
Funding Amount
$187,925.00
Summary
Chromosome translocation, in which breaks occur in two chromosomes and rejoin to form two new hybrid chromosomes, is a common genetic alteration in leukaemia. Translocations have been invaluable in identifying genes important in the development of leukaemia. The genetic consequence of translocation is either the deregulation of critical genes adjacent to the breakpoints or the formation of new hybrid genes with novel properties. We have identified the genes at the breakpoints of a T-cell leukaem ....Chromosome translocation, in which breaks occur in two chromosomes and rejoin to form two new hybrid chromosomes, is a common genetic alteration in leukaemia. Translocations have been invaluable in identifying genes important in the development of leukaemia. The genetic consequence of translocation is either the deregulation of critical genes adjacent to the breakpoints or the formation of new hybrid genes with novel properties. We have identified the genes at the breakpoints of a T-cell leukaemia translocation involving chromosomes 4 and 11. The chromosome 11 gene, NUP98, is known to be involved in two other translocations in acute myeloid leukaemia but not in T-cell leukaemia. The chromosome 4 gene RAP1GDS has not been previously shown to be involved in human cancer. This project seeks to understand how the fusion protein NUP98-RAP1GDS (NRG) plays a role in the origin of leukaemia.Read moreRead less
Investigating Tumour Maintenance Using Regulated RNA Interference
Funder
National Health and Medical Research Council
Funding Amount
$511,294.00
Summary
Inhibiting gene expression using the recently discovered process known as RNA interference (RNAi) can be used as an experimental tool to analyse specific genes, in cells and genetically engineered animal models of human disease. I propose to validate potential drug targets in cancer by using RNAi to inhibit specific genes in established mouse tumours. A further aim is to use RNAi to mimic human cancer gene mutations in mouse cancer models, to discover novel tumour suppressor genes.