Progesterone Receptor Action In The Normal Human Breast
Funder
National Health and Medical Research Council
Funding Amount
$360,500.00
Summary
Breast cancer affects 10000 Australian women annually and is a major cause of cancer-related death. The hormone progesterone, which is produced by the ovaries in women, is responsible for many aspects of normal breast development and function. Progesterone is also a major component of hormone replacement therapy (HRT) and oral contraceptives (OCP), which are taken by millions of women worldwide. It has been established that the use of HRT and OCP containing progesterone-like hormones leads to in ....Breast cancer affects 10000 Australian women annually and is a major cause of cancer-related death. The hormone progesterone, which is produced by the ovaries in women, is responsible for many aspects of normal breast development and function. Progesterone is also a major component of hormone replacement therapy (HRT) and oral contraceptives (OCP), which are taken by millions of women worldwide. It has been established that the use of HRT and OCP containing progesterone-like hormones leads to increased breast cancer risk, yet the ways in which this happens are not known. Breast cancer is thought to begin early in a woman's life, with a number of genetic changes that accumulate over a period of many years; the majority of breast malignancies are not diagnosed until after the age of 50. However, there are recent indications that some areas of apparently normal breast have undergone a few genetic changes, even in women with no evidence of malignancy, but there is nothing known about how progesterone may affect these areas and possibly encourage breast cancer development. This project will firstly explore the influence of progesterone on the normal breast, to clarify how this hormone acts in normal cells. We will then investigate the involvement of progesterone in areas of normal breast that have undergone genetic alterations. This will determine whether one way in which progesterone may increase breast cancer risk is by affecting the behaviour of cells with genetic changes to make them more likely to develop further changes and subsequently progress to full cancer development. If women are to continue to derive the benefits of progesterone exposure, there is a compelling need to appreciate how progesterone acts in the normal breast and how it increases breast cancer risk. Achievement of the aims of this project will provide invaluable knowledge and greatly increase our understanding in this area.Read moreRead less
Factors Regulating The Temporal And Spatial Assembly Of G-protein Coupled Receptor-mediated Arrestin Complexes
Funder
National Health and Medical Research Council
Funding Amount
$472,770.00
Summary
G-protein coupled receptors are proteins that are present at the surface of most cells in the human body. They recognise and bind to specific molecules, such as hormones, the act of which results in a specific signal being transmitted into the cell. This signal alters the function of the cell and so it is critical that it is appropriate, both in type and duration. G-protein coupled receptors and the molecules that activate them provide an essential function within the human body for communicatin ....G-protein coupled receptors are proteins that are present at the surface of most cells in the human body. They recognise and bind to specific molecules, such as hormones, the act of which results in a specific signal being transmitted into the cell. This signal alters the function of the cell and so it is critical that it is appropriate, both in type and duration. G-protein coupled receptors and the molecules that activate them provide an essential function within the human body for communicating between cells, and consequently between organs. They are a major mechanism by which nerve signals are transmitted and hormones regulate bodily functions. They are therefore an important target for pharmaceuticals, with up to 50% of ethical drugs and many drugs of abuse acting upon them. It is critical to understand how these receptors alter cellular function once they receive an appropriate signal, but it is also essential to know how such responses are switched off. Arrestins are proteins within cells that interact with G-protein coupled receptors to 'arrest' their signalling. They desensitise the cell to continuous stimulation, but also act to resensitise the cell to respond to future, separate signals. Recently, they have also been shown to provide alternative mechanisms of altering cellular activity by interacting with other cellular proteins. These interactions greatly increase the potential ways in which a cell can respond once a G-protein coupled receptor is activated. Understanding the resulting complexity is essential if we are to fully exploit the vast therapeutic potential of this important receptor family.Read moreRead less