Role Of Insulin-like Growth Factor Binding Protein-3 As A Mediator Of Apoptosis In Human Breast Cancer
Funder
National Health and Medical Research Council
Funding Amount
$352,234.00
Summary
Human breast cancer, like other human cancers, is characterised by a disruption of normal cellular growth due to defects in the control of both cell proliferation and cell death. Understanding how these processes are regulated in normal and cancerous breast cells is an important goal for breast cancer treatment. Insulin-like growth factor binding protein (IGFBP)-3 is a regulator of normal and cancerous breast cell growth and has been implicated as a negative prognostic indicator for breast cance ....Human breast cancer, like other human cancers, is characterised by a disruption of normal cellular growth due to defects in the control of both cell proliferation and cell death. Understanding how these processes are regulated in normal and cancerous breast cells is an important goal for breast cancer treatment. Insulin-like growth factor binding protein (IGFBP)-3 is a regulator of normal and cancerous breast cell growth and has been implicated as a negative prognostic indicator for breast cancer progression. IGFBP-3 inhibits the growth of breast cancer cells and causes them to die by a process called apoptosis. We are determining how IGFBP-3 causes breast cancer cells to die by apoptosis. In particular, we are investigating whether IGFBP-3 may make breast cancer cells more sensitive to the apoptotic effects of ionising radiation and chemotherapeutic drugs which are both current therapies for the treatment of breast carcinoma. These studies may, in turn, elucidate the mechanisms that lead to increased resistance of breast cancers to these treatments.Read moreRead less
Insulin-like Growth Factor (IGF)-II Binding Specificity Of IGF Binding Protein-6: Structural And Functional Studies.
Funder
National Health and Medical Research Council
Funding Amount
$265,630.00
Summary
Insulin-like growth factor II (IGF-II) is a protein which is involved in normal growth. However, in some circumstances it may also stimulate cancer growth. IGF binding protein-6 (IGFBP-6) binds to IGF-II and stops its activity. One of the major challenges of modern biology is understanding why some proteins bind to other proteins. Proteins fold in various ways and have specific three-dimensional structures. Two proteins which bind strongly to each other have structures which fit each other like ....Insulin-like growth factor II (IGF-II) is a protein which is involved in normal growth. However, in some circumstances it may also stimulate cancer growth. IGF binding protein-6 (IGFBP-6) binds to IGF-II and stops its activity. One of the major challenges of modern biology is understanding why some proteins bind to other proteins. Proteins fold in various ways and have specific three-dimensional structures. Two proteins which bind strongly to each other have structures which fit each other like a 'lock and key'. The aim of this project is to understand how IGFBP-6 binds to IGF-II by looking at its three-dimensional structure. Using this information, it may be possible to develop new treatments which can inhibit IGF-II activity and therefore may be useful in the treatment of some cancers.Read moreRead less
Insulin-like Growth Factor Binding Protein-3 (IGFBP-3) Sensitivity And Signalling In Breast Cancer
Funder
National Health and Medical Research Council
Funding Amount
$414,343.00
Summary
The growth of all tissues in the body depends on many growth factors, hormones and other proteins which work together to control cell division. Some of these factors stimulate the division of the cells which make up the body tissues, and some inhibit it, so that a balance of these stimulators and inhibitors ensures that tissues do not grow too fast, or too large. The development of breast cancer and the growth of breast tumours is thought to be due to uncontrolled or faulty actions of the protei ....The growth of all tissues in the body depends on many growth factors, hormones and other proteins which work together to control cell division. Some of these factors stimulate the division of the cells which make up the body tissues, and some inhibit it, so that a balance of these stimulators and inhibitors ensures that tissues do not grow too fast, or too large. The development of breast cancer and the growth of breast tumours is thought to be due to uncontrolled or faulty actions of the proteins and hormones which regulate the way breast cells multiply. One protein which normally regulates the division of breast cells is IGFBP-3. We have found that in some breast cancer cells, IGFBP-3 is no longer able to inhibit cell division, and this may lead to tumour growth and invasion of other tissues. We are interested in finding out how IGFBP-3 normally controls breast cell proliferation, and why some breast cancers are resistant to IGFBP-3. To do this, we will use normal breast cells in culture to examine how IGFBP-3 interacts with other cellular factors to prevent cell division. We will then look at whether the breast cancer cells have changed so that they are no longer able to recognise IGFBP-3 as an inhibitory protein. This may be because of changes in the way IGFBP-3 binds to the breast cancer cell, or because of changes in the way it interacts with other proteins in the cell. Because IGFBP-3 is made by normal and breast cancer cells, we will also study whether the IGFBP-3 being made by breast cancer cells is normal, or if it changed in some way that makes it inactive. By understanding why some breast cancers are not inhibited by IGFBP-3, we will be able to design new and better methods of preventing, detecting and treating the growth of all breast tumours.Read moreRead less
Compared with normal-weight children, obese youth have a higher chance of developing diseases like Type 2 diabetes. With 1 in 4 Australian children now being overweight or obese, effective treatment programs need to be developed alongside those aimed at prevention. This program of research aims to identify which overweight/obese children are most likely to develop diabetes, with a particular focus on how infant nutrition regulates important growth factors to alter long-term diabetes risk.
Pathways Involved In The Insulin-like Growth Factor (IGF)-independent Actions Of IGF Binding Protein-6
Funder
National Health and Medical Research Council
Funding Amount
$550,725.00
Summary
Insulin-like growth factors (IGFs) are important proteins that regulate growth. When not regulated properly, diseases such as cancer can occur. A family of IGF binding proteins regulates IGFs. IGFBPs may inhibit IGFs and we have shown that one of them, IGFBP-6, decreases growth of some experimental cancers. As well as regulating IGFs, some IGFBPs alter cell behaviour independently of IGFs, and we found that IGFBP-6 stimulates cell movement in this way. We will now determine how this happens.