Grant: Doctoral Award - Frederick Banting and Charles Best Canada Graduate Scholarships

Breast cancers are extremely complex diseases with fatal outcomes in thousands of women annually in Canada and millions worldwide. In any single person, the prognosis is affected by many factors. This is due, in part, to the fact that breast cancers destined to be fatal, even with the best current therapies, have already become very diverse by the time they are diagnosed. It is generally assumed that eliminating all of the malignant cells capable of causing a relapse will require targeting changes that develop in the first cells to acquire malignant properties, regardless of any later changes that appear in their daughter cells. The objective of this proposal is therefore to characterize these initial changes. To make this possible, I will investigate human breast cancer cells that are experimentally produced using a defined protocol. According to this protocol, a special strain of immunodeficient mice are transplanted with normal human mammary cells into which a mutant cancer-causing gene has just been introduced. Our lab has found that within 2 weeks after being transplanted into mice, the genetically altered cells are already exhibiting abnormal growth and protein expression properties. In addition, our lab has obtained a complete description of the molecules that control the genes expressed in the different types of normal human cells from which tumours can be obtained, as well as a picture of how these molecules interact with DNA to control gene expression - like fingers on a keyboard producing different chords of music. I propose to similarly characterize 2-week post-transplant cells from our engineered human breast cancer model and identify how these molecules contribute to breast cancer development by genetically manipulating their activity. The results will provide new information about the identity and role of very early changes that contribute to human breast cancer development and thus set the stage for the discovery of new therapeutic agents.