The Role Of Protease-activated Receptor-2 In Regulation Of Bone Metabolism
Funder
National Health and Medical Research Council
Funding Amount
$216,100.00
Summary
Many diseases of bones, such as osteoporosis and delayed fracture repair, result from the abnormal function of bone cells. Factors regulating bone cell function are, therefore, important in maintaining a healthy skeleton, as well as in the skeleton's response to disease. We have recently demonstrated the presence of a receptor called PAR-2 on bone-forming cells. We have also shown that activation of PAR-2 inhibits the development of bone-resorbing cells (osteoclasts) in response to hormones. We ....Many diseases of bones, such as osteoporosis and delayed fracture repair, result from the abnormal function of bone cells. Factors regulating bone cell function are, therefore, important in maintaining a healthy skeleton, as well as in the skeleton's response to disease. We have recently demonstrated the presence of a receptor called PAR-2 on bone-forming cells. We have also shown that activation of PAR-2 inhibits the development of bone-resorbing cells (osteoclasts) in response to hormones. We plan to investigate the mechanism of this effect, as well as to identify how PAR-2 activation modulates other responses of bone cells to hormones. Molecules that activate PAR-2 are present in bone in certain disease situations, but it is not known what activates PAR-2 in bone under normal conditions. We will identify physiological activators of PAR-2 within bone.Read moreRead less
Hormonal Influences In The Pathogenesis Of Ovarian Tumours
Funder
National Health and Medical Research Council
Funding Amount
$264,601.00
Summary
Ovarian cancer is one of the most common malignancies affecting the female reproductive system. We have found that two types of tumour of the ovary produce a hormone called inhibin; these tumours are also known to produce the steroid hormone estrogen. In these studies we are seeking to determine the genetic changes in the tumours that cause the production of these hormones. We suspect that these genetic changes are also the same changes which contribute to the development of the cancers. In orde ....Ovarian cancer is one of the most common malignancies affecting the female reproductive system. We have found that two types of tumour of the ovary produce a hormone called inhibin; these tumours are also known to produce the steroid hormone estrogen. In these studies we are seeking to determine the genetic changes in the tumours that cause the production of these hormones. We suspect that these genetic changes are also the same changes which contribute to the development of the cancers. In order to identify these genes we will draw on our knowledge of the genes that are important in the controlof growth and hormone secretion in normal ovarian cells. To assist this molecular analysis we will use two ovarian cell lines in culture that have many of the features of the primary tumours including inhibin secretion. We will also use new techniques to scan over 500 genes involved in tumours in general to see whether we detect any unusual or distinctive patterns in this sub-group of tumours. A genome wide scanning technique will be used to seek changes in the DNA of the tumours, inparticular loss of genetic material or amplification of regions. Identification of the genetic changes within these tumours should enable better systems of classification, enhance prognostication and provide specific targets for the development of appropriate treatment strategies.Read moreRead less
Role Of The Nuclear Growth Hormone Receptor In Cell Proliferation And Function
Funder
National Health and Medical Research Council
Funding Amount
$477,750.00
Summary
In addition to final height, growth hormone regulates many tissues in the body, and through these, regulates metabolism, body composition, vitality and aspects of ageing. However, there is some evidence that GH can also promote cancer, notably colon and blood cell cancers. Our discovery of the receptor for growth hormone in the cell nucleus, notably in many cancers, has led us to investigate the role of the nuclear GH receptor. We have found that targeting this receptor to the nucleus allows the ....In addition to final height, growth hormone regulates many tissues in the body, and through these, regulates metabolism, body composition, vitality and aspects of ageing. However, there is some evidence that GH can also promote cancer, notably colon and blood cell cancers. Our discovery of the receptor for growth hormone in the cell nucleus, notably in many cancers, has led us to investigate the role of the nuclear GH receptor. We have found that targeting this receptor to the nucleus allows the cell to divide without the need for the normal factors which initiate cell division and survival. We have also found that a part of the GH receptor acts as a gene activator, and have identified some of the nuclear proteins which bind to the receptor and make this so. This proposal aims to establish the link between the nuclear GH receptor and cell division, both mechanistically, and in live animals. We also plan to establish if nuclear localizing the receptor artificially results in cancer formation. The outcome would provide an index of risk from current GH therapy, and could lead to a new cancer therapy.Read moreRead less