Published in the leading scientific journal, Nature, this exciting study shows that introducing a single gene into cells isolated from normal human breast tissue can cause rapid development of breast cancer. This work is important because it allows researchers, for the first time, to examine in a controlled way the early cellular changes that lead to the development of breast cancer from initially normal human breast cells.
During the earliest stages in the development of cancer, the genetic changes that take place are likely to be permanently retained by all subsequent cancer cells. Knowing how these change cell behaviour could provide new indicators that a cancer is arising. They could also be ideal targets for cancer therapy, since they are likely to be present in all of the cells in a full-blown cancer.
Although most naturally-arising tumours in people initially develop from a single cell, by the time a detectable tumour has formed, it usually already contains a mixture of cells that have different features. These cells may respond differently to current therapies. Scientists have therefore been interested in trying to develop new ways to determine how these different features are acquired.
In this study, researchers at the BC Cancer Agency’s Terry Fox laboratory combined their expertise in isolating different types of normal human breast cells and introducing mutant genes into them together with a novel method called DNA barcoding. Each individual cell was labeled with a different permanent “DNA barcode,” making it possible for the first time to track simultaneously the subsequent growth of many different individually transformed cells.
The cells carrying different mutant genes were then transplanted into special mice that lack an immune system. This animal model was very important as it allowed the researchers to examine the cells even before a breast cancer developed as well as later after tumours became apparent.
To the surprise of the scientists, tumours appeared rapidly and repeatedly even when the cancer was produced from normal breast cells that had taken up a single cancer-causing gene. This disproved a longstanding assumption that the development of human breast cancer requires a long time to accumulate multiple genetic changes. This method was also highly reproducible and tumours consistently began to appear about eight weeks after the cells were transplanted.
According to Eaves, this very same process can now be widely used to perform experiments that were previously thought to be impossible, allowing scientists to study the earliest cellular changes that cause a normal human breast cell to become malignant. This method may also prove useful for analyzing the initial stages of development of other types of human cancers.
The potential for this approach to bring about improved cancer treatments is also now being explored since these can now be tested on breast cancer cells at different stages during their formation.
This research received 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 study is available from Nature here