Scientists in the Faculty of Medicine and the BC Cancer Agency used a single mutant gene to create breast cancer in mice, upending a longstanding assumption that development of human breast cancer requires a long time to accumulate multiple genetic changes. The finding is an important advance toward understanding the cellular changes that can lead to human breast cancer.
Led by Connie Eaves, professor in the Department of Medical Genetics at UBC and a distinguished scientist at the BC Cancer Agency, the research team inserted a mutant gene into normal human breast tissue cells and then implanted those cells in mice, where they formed tumors. Researchers used DNA barcoding to track the growth of many individually transformed cells after they were transplanted into a single mouse and were able to observe how the breast cells change even before they became fully malignant. Professor Eaves asserts that this approach makes it feasible to study the initial changes that cause a normal human breast cell to become malignant, and this methodology can be used to perform experiments that were previously thought to be impossible and potentially bring about improved outcomes based on the identification of early changes that should be shared by all cells in a given breast tumor. By the time a breast cancer first becomes apparent, it usually already contains a mixture of cell populations with different features and different responses to existing therapies. It has therefore been difficult to determine how these different features are acquired.
The research was performed at the BC Cancer Agency’s Terry Fox Laboratory with funding from the Canadian Cancer Society Research Institute, the Canadian Breast Cancer Foundation, the Canadian Breast Cancer Research Alliance, and the Canadian Institutes of Health Research.
The findings, “Barcoding reveals complex clonal dynamics of de novo transformed human mammary cells,” are published in Nature, available at www.nature.com/nature/journal/v528/n7581/full/nature15742.html (paywall).
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