The Identification Of Novel Genes Involved In The Initiation And Development Of Thyroid Neoplasia
Funder
National Health and Medical Research Council
Funding Amount
$227,545.00
Summary
Thyroid cancer is the most frequently diagnosed endocrine malignancy, comprising 1% of all human malignancy. However, its actual occurrence indicated by autopsy studies may be as high as 10%. To date, a number of genes, both oncogenes (genes that are inappropriately switched on and take part in the process of tumour development) and tumour suppressor genes (genes that are switched off and lose their protective role against tumour development), have been implicated in the development of thyroid c ....Thyroid cancer is the most frequently diagnosed endocrine malignancy, comprising 1% of all human malignancy. However, its actual occurrence indicated by autopsy studies may be as high as 10%. To date, a number of genes, both oncogenes (genes that are inappropriately switched on and take part in the process of tumour development) and tumour suppressor genes (genes that are switched off and lose their protective role against tumour development), have been implicated in the development of thyroid cancer. However mutations, mistakes in the genetic code, of these genes account for only a small percentage of thyroid tumours and none of these genes have been shown to be useful as clear prognostic markers for tumour progression or aggressiveness. The merging of the 2 fields of cytogenetics (the study of chromosomes) and molecular genetics (the study of genes at the DNA and RNA level) has strengthened our ability to understand the process of tumour development. We are proposing use of a technique called Comparative Genomic Hybridisation to aid in the identification of new genes associated with tumour development in both benign and malignant thyroid disease. This technique has already been used to aid in the location of genes with a role in ovarian and brain cancer and in some familial syndromes characterised by breast and gastrointestinal malignancies. This method involves the detection of regions of chromosomal amplifications or deletions in tumour DNA that is fluorescently labelled (green), mixed with normal human DNA also fluorescently labelled (red). If the tumour contains regions of amplification (likely housing an oncogene), analyses show increased green fluorescence and if deletions are present (likely housing a tumour suppressor gene), analyses show increased red fluorescence. Chromosomal regions identified by this method will be further analysed to identify the precise genes they contain and establish a role for these genes in the development of thyroid tumours.Read moreRead less
Understanding The Development Of Pancreatic Islet Cell Tumours
Funder
National Health and Medical Research Council
Funding Amount
$579,163.00
Summary
We will use mouse models of pancreatic cancer that we have established previously to investigate the molecular basis of the development and progression of tumours in the insulin-producing cells of the pancreas. We propose to manipulate a small number of candidate genes using established islet cultures and new mouse models in order to characterise the effect they have on islet cell biology and tumorigenesis.
Transcriptional Targets Of The MEN1 Tumour Suppressor In Endocrine Cancer
Funder
National Health and Medical Research Council
Funding Amount
$454,500.00
Summary
We have developed mouse models of a human cancer syndrome called multiple endocrine neoplasia type 1 (MEN 1) by inactivating the tumour suppressor gene responsible. These mice devlop tumours of a wide variety of different tissues, including the pancreas, pituitary, parathyroids and gonads. The data obtained from this project will be the first major step towards determining the mechanism by which the Men1 gene functions as a tumour suppressor and should shed light on its role in normal cell cycle ....We have developed mouse models of a human cancer syndrome called multiple endocrine neoplasia type 1 (MEN 1) by inactivating the tumour suppressor gene responsible. These mice devlop tumours of a wide variety of different tissues, including the pancreas, pituitary, parathyroids and gonads. The data obtained from this project will be the first major step towards determining the mechanism by which the Men1 gene functions as a tumour suppressor and should shed light on its role in normal cell cycle regulation. Findings from murine models of endocrine cancer will lead to a better understanding of MEN 1 in particular, and also of carcinogenesis in general. Defining the cellular pathways normally disrupted by loss of the MEN 1 gene will be useful in designing therapeutic approaches to control endocrine tumours and some other types of cancer.Read moreRead less
Identification Of Novel Regulators Of Flt3 Receptor-dependent Dendritic Cell Development And Differentiation
Funder
National Health and Medical Research Council
Funding Amount
$605,043.00
Summary
Dendritic cells are specialized immune cells that play a key role in regulating the immune system. In the resting animal, their differentiation is largely regulated by signalling though the Flt3 pathway - the pathway most frequently dysregulated in leukemias. This project will generate a a detailed map of the important signals that instruct dendritic cell development along the Flt3 pathway and provide improved understanding of the cellular and molecular controls of this pathway.