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
Bombesin Like Peptides As Autocrine Growth Factors In Colorectal Cancer
Funder
National Health and Medical Research Council
Funding Amount
$406,980.00
Summary
Colorectal carcinoma (cancer of the large bowel) is the second most common cause of cancer death. Colorectal carcinomas in common with other cancer types such as cancer of the prostate and lung often produce its own growth factors and receptors. Activation of the receptor by the growth factor further stimulates the tumour's growth and spread throughout the body. The objective of this project is to determine the potential roles of a growth factor termed Bombesin Like Peptide. This peptide, now kn ....Colorectal carcinoma (cancer of the large bowel) is the second most common cause of cancer death. Colorectal carcinomas in common with other cancer types such as cancer of the prostate and lung often produce its own growth factors and receptors. Activation of the receptor by the growth factor further stimulates the tumour's growth and spread throughout the body. The objective of this project is to determine the potential roles of a growth factor termed Bombesin Like Peptide. This peptide, now known as GRP in mammalian systems, is an established growth factor in certain lung cancers but little is known about its role in tumours of the large bowel. We will study the expression and production of GRP and its receptors at the gene and protein level, the ability of GRP to stimulate growth, the chemical structures of GRP, and the potential of antagonists of GRP to modulate growth. Studies will be performed in patients with bowel cancer, in animal models of bowel cancer, and with bowel tumours removed from patients and bowel cancer cell lines. A successful outcome will result in the development of assays for the early diagnosis and monitoring of bowel cancer and the potential for novel treatments such as GRP receptor antagonists and radiolabelled GRP analogues for radiotherapy.Read moreRead less