Tumour Suppressor Networks: The Role Of SHIP-1 And Lyn In Suppressing Haematopoietic Tumours
Funder
National Health and Medical Research Council
Funding Amount
$469,526.00
Summary
Haematopoietic malignancies kill a large number of Australians each year. Improving our understanding of the molecular mechanisms that underlie these diseases is essential for the design of more effective treatments. Lyn and SHIP-1 are enzymes that are found in blood cells, and both participate in terminating cellular responses. As such, these enzymes are critically important for maintaining stability in the immune system. While these enzymes have unique roles, we also have good evidence that in ....Haematopoietic malignancies kill a large number of Australians each year. Improving our understanding of the molecular mechanisms that underlie these diseases is essential for the design of more effective treatments. Lyn and SHIP-1 are enzymes that are found in blood cells, and both participate in terminating cellular responses. As such, these enzymes are critically important for maintaining stability in the immune system. While these enzymes have unique roles, we also have good evidence that in some instances Lyn and SHIP-1 participate in the same biochemical pathway. We have created mice that are unable to make Lyn protein, and have found that these mice develop blood cell tumours. Mice lacking SHIP-1 develop a number of haematological defects, but die at a young age due to an inflammatory lung condition, making an assessment of the role of SHIP-1 in age-dependent tumour development difficult. We now wish to study the role of SHIP-1 in tumour development, by generating mice that lack SHIP-1 in specific white blood cell compartments. We are also investigating how SHIP-1 and Lyn cooperate in tumour suppression, and we have recently generated mice that simultaneously lack both SHIP-1 and Lyn. Preliminary studies indicate that compound mutant mice develop multiple haematological malignancies. We will fully characterize tumour development in these animals, and determine the molecular basis for this pathology. We will focus on two pathways that have been previously implicated in oncogenesis. These studies will improve our insight into how Lyn and SHIP-1 cooperate in blood cell development, cellular homeostasis and oncogenesis, and add to our biological and biochemical understanding of tumour suppressor networks.Read moreRead less
Proteomic Screening For Apoptotic Markers In Breast Cancer
Funder
National Health and Medical Research Council
Funding Amount
$531,696.00
Summary
The induction of apoptosis, or programmed cell death, is a key factor in the response of tumours to chemotherapeutic agents and ionising radiation; therefore biological markers that predict the clinical outcome to these therapies are needed. Over the past 2 years, our laboratory has developed techniques of protein analysis to evaluate changes in proteins during apoptosis caused by chemotherapeutic agents. Preliminary protein profiling studies of apoptosis induction in human breast cancer cell li ....The induction of apoptosis, or programmed cell death, is a key factor in the response of tumours to chemotherapeutic agents and ionising radiation; therefore biological markers that predict the clinical outcome to these therapies are needed. Over the past 2 years, our laboratory has developed techniques of protein analysis to evaluate changes in proteins during apoptosis caused by chemotherapeutic agents. Preliminary protein profiling studies of apoptosis induction in human breast cancer cell lines showed time-dependent decreases in two proteins, identified as S100A6 and ubiquitin. Both are known to be important in cell function. In the proposed project we will build on our preliminary findings to provide important new information central to the understanding of cancer cell biology and apoptosis in addition to evaluating the ability of anti-cancer treatments to induce apoptosis. Using a combination of protein analysis technologies, this project has the potential to provide reliable and novel biomarkers which will indicate the efficacy and selectivity of anti-cancer treatments in inducing tumour cell death. The knowledge gained in this project will aid clinical assessment of the response to cancer treatment(s) in patients in the form of specific screening assays, and may result in identification and development of effective new agents for cancer treatment and prevention. Furthermore, the outcomes of this project will increase our understanding of fundamental cancer cell biology and apoptosis.Read moreRead less
The Human Papilloma Virus Oncoprotein E7 Degrades The Retinoblastoma Protein By Enhancing Calpain Activity
Funder
National Health and Medical Research Council
Funding Amount
$258,067.00
Summary
Cervical cancer is the second most prevalent cancer worldwide and the fifth leading cause of cancer deaths in women. Approximately 470,000 new cases are diagnosed annually. In most cases cervical cancer is thought to be caused by certain types of the human papillomavirus. Human papillomavirus makes a seies of proteins that cause the destruction of key host proteins in the cells they infect. This destruction is central to the formation of cervical cancer. We have recently discovered that we can p ....Cervical cancer is the second most prevalent cancer worldwide and the fifth leading cause of cancer deaths in women. Approximately 470,000 new cases are diagnosed annually. In most cases cervical cancer is thought to be caused by certain types of the human papillomavirus. Human papillomavirus makes a seies of proteins that cause the destruction of key host proteins in the cells they infect. This destruction is central to the formation of cervical cancer. We have recently discovered that we can prevent this destruction and rescue the key host proteins using inhibitors of the enzyme calpain. Here we seek to determine whether calpain inhibitors could find application in the treatment of human papillomavirus associated cancer.Read moreRead less