Excerpted with permission from University of Guelph Research Magazine, Spring 2008.
A Guelph researcher is determined to make treatments for breast cancer more effective. He’s examining the relationship between the onset of breast cancer and over expression of certain signaling proteins, which may transform normal mammary epithelial cells and induce mammary tumours.
Prof. Roger Moorehead, Department of Biomedical Sciences, is interested in how cell receptors – proteins found on the cell surface that recognize specific molecules – interact in causing mammary tumours and how these receptors may serve as therapeutic targets.
The main receptor being investigated is the insulin-like growth factor receptor (IGF-1R), which is thought to play an important role in breast cancer development. Another receptor in question is Her-2, which can also lead to mammary tumor formation. It has been shown that the insulin-like growth factor plays an important role in the development of breast cancer, although the exact pathway in human and animal models is not known,” says Moorehead. “We hope to uncover this pathway to be able to produce agents that are more effective at targeting breast cancer.”
To help determine the role of the IGF-1R in breast cancer, he and a team of researchers have created a transgenic mouse, an animal model that allows them to control the expression of the IGF-1R in mammary epithelial cells. So far, they’ve discovered the development of mammary tumours occurs rapidly when the IGF-1R is expressed.That’s because the receptor induces uncontrolled cell proliferation and prevents apoptosis (programmed cell death), a common control against uncontrolled cell growth. With these cellular changes created by the IGF-1R, tumour cells grow uncontrollably. It is also suspected that the IGF-1R can activate other tumour-inducing receptors, including Her-2.
Therapies exist that target the Her-2 receptor – which, like the IGF-1R, leads to cell proliferation and prevents apoptosis. But many tumours gain the ability to overcome this therapy by up-regulating the expression of the IGF-1R. This finding has triggered researchers to study the interaction between the IGF-1R and Her-2 and how their relationship is helping tumours become resistant to existing therapies. This is particularly important because research suggests that 20 to 30 per cent of breast cancers over express. Moorehead says this research will provide information about the effectiveness of IGF-1R therapeutic treatments for breast cancer, which are currently in early-stage clinical trials.
With this advancement, researchers will have expanded knowledge of how tumours form and grow so they can develop more effective targets for treatment. Collaborators from the University of Guelph on this research project include Prof. Jim Petrik, Department of Biomedical Sciences, and graduate students Rob Jones and Craig Campbell.
Infrastructure for this area of research was funded by the Canada Foundation for Innovation and the Ontario Research Fund. The research program is funded by the Canadian Institutes of Health Research, the Canadian Breast Cancer Alliance, the Canadian Breast Cancer Foundation – Ontario Region and the Cancer Research Society.
The infrastructure for this project was partially funded by the Canada Foundation for Innovation.