Characterisation Of A Novel Prostate-expressed Kallikrein-like Protease And Its Target Proteins
Funder
National Health and Medical Research Council
Funding Amount
$724,544.00
Summary
Prostate disease is common in most men in later life and can affect their quality of life adversely. The primary conditions are benign prostatic hyperplasia or BPH and prostate cancer. Symptoms of BPH affect between 50-70% of men over the age of 50 and prostate cancer is now the most common internal cancer diagnosed in men. More importantly, prostate cancer is the second most common cause of cancer deaths. We don't yet fully understand exactly how these diseases occur but the male sex hormones o ....Prostate disease is common in most men in later life and can affect their quality of life adversely. The primary conditions are benign prostatic hyperplasia or BPH and prostate cancer. Symptoms of BPH affect between 50-70% of men over the age of 50 and prostate cancer is now the most common internal cancer diagnosed in men. More importantly, prostate cancer is the second most common cause of cancer deaths. We don't yet fully understand exactly how these diseases occur but the male sex hormones or androgens are known to play an important role. Prostate specific antigen or PSA has become widely accepted as a useful tool in helping to detect prostate cancer and then monitoring the disease. PSA, which is regulated by androgens, is an enzyme that either activates or breaks down many proteins that are important in both the normal function of the prostate and in the development of cancer. PSA belongs to a family of enzymes called the kallikreins. We have recently discovered a new member of this family that, like PSA, is also found in the prostate. We have called this new enzyme, K6, as it is the sixth member of this family to be identified. So , this project is about characterising this new K6 enzyme, finding out if it is also found in the prostates of men with BPH and prostate cancer, whether it is also regulated by androgens and what sort of proteins it may activate in these diseases. We will also compare these findings with what we know about PSA in these diseases. From these studies, we will not only understand more about this K6 enzyme and how it might be important in the prostate but also how it relates to PSA. These findings may ultimately lead to some new approaches in the detection and treatment for BPH and prostate cancer.Read moreRead less
The Role Of Ghrelin And Growth Hormone Releasing Hormone In The Autocrine Regulation Of Prostate Cancer Cell Growth
Funder
National Health and Medical Research Council
Funding Amount
$240,990.00
Summary
Insulin-like growth factor-I (IGF-I) is an important growth factor with a major role in the growth and development of many normal and tumour cells. Its production is controlled by growth hormone (GH), released from the pituitary gland at the base of the brain. GH releasing hormone (GHRH), a hormone released from higher centres in the brain, regulates the production of GH itself and now it is recognised that a second pathway, the ghrelin-GH secretagogue receptor (GHS-R) axis is also important in ....Insulin-like growth factor-I (IGF-I) is an important growth factor with a major role in the growth and development of many normal and tumour cells. Its production is controlled by growth hormone (GH), released from the pituitary gland at the base of the brain. GH releasing hormone (GHRH), a hormone released from higher centres in the brain, regulates the production of GH itself and now it is recognised that a second pathway, the ghrelin-GH secretagogue receptor (GHS-R) axis is also important in regulating GH release. There is growing evidence that the GHRH-GH-IGF axis has a significant role in prostate cancer, but little is known about how this happens. We also have evidence that the ghrelin-GHS-R axis is involved in prostate cancer, as prostate cancer cell lines produce both ghrelin and the receptor through which it acts. Our preliminary studies show that ghrelin enhances cell growth in these cells. GHRH blocking agents (antagonists) are potential treatments for prostate cancer, as they slow the growth of prostate tumours. How they act is unclear, but they might interfere with a locally active GHRH pathway in the prostate. This study aims to explore the role of ghrelin and GHRH in prostate cancer. Since there is an increase in the use of GHRH, GH and-or IGF-I and potentially ghrelin for the treatment of a variety of medical conditions, including some in the aging male, the need for a fuller understanding of the role of this axis in prostate cancer is increasingly important. Such information will lead to a deeper understanding of the actions of ghrelin and GHRH and provide potential opportunities for design of new therapies for prostate and other GH-IGF-responsive tumours.Read moreRead less
Characterising The Beneficial Effects Of Estrogen On The Prostate Gland
Funder
National Health and Medical Research Council
Funding Amount
$594,722.00
Summary
Prostate cancer is hormonally regulated and currently managed by androgen ablation. This application seeks to study the potential benefits of estrogen action for the treatment of prostate disease, including PCa. We will show estrogen hormone action causes prostatic cell death, targeting the stem-progenitor cells so the treated prostatic tissue does not regenerate. This project will provide pre-clinical proof of the efficacy of estrogenic compounds as a potential therapy for prostate disease.