In a cancerous breast, researchers have seen the problems with the various components of breast tissue and could not fully explain why they happened. The tissue, called the stroma, includes fat cells that provide padding; fibroblasts, which make the framework for tissue; pericytes in blood vessels, which are contractile cells that help regulate blood pressure; as well as myoepithelial cells comprising the outer layer of the ductal system through which milk flows.
The fact that human breast cancer precursor cells remain to be elucidated has hampered cancer research greatly. Now, a study from researchers at Augusta University shows that when mutated, a gene known for its ability to repair DNA, appears to instead cause breast cancer. The team state that the gene, GT198, whether mutated by genetics and/or environmental factors, has strong potential as both as a way to diagnose breast cancer early and as a new treatment target.
Previous studies show that all cells have the GT198 gene, however, most adult cells don’t express it. In the breast it may be transiently expressed in a pregnant woman preparing for milk production and, potentially, in the case of breast injury. Earlier studies from the lab identified tumour cells containing mutated GT198 protein in various types of ovarian cancer. Subsequent studies by the group and others have shown it has multiple roles that also include regulating stem cells, cell suicide and turning other genes off and on. Mutations of the gene are known to be present in both early onset breast and ovarian cancer. The current study shows that the stem, or progenitor cells, which should ultimately make healthy breast tissue, can also have GT198 mutations that prompt them to instead make a perfect bed for breast cancer.
The current study investigated an international sample of 254 cases of breast cancer in pre- and postmenopausal women. Results show once mutated, GT198 can enable tumour production without hormone-regulation. Data findings show that this gene mutation can be in both the blood and the tumour tissue of patients where it is found in high percentages. The team hypothesize that once this gene is mutated, it induces the tumour to grow.
The lab state that the mutated GT198 also directly affects stem cells found on blood vessels that make these various components of breast tissue. They go on to add that their data show it’s a new target in cancer that affects all the different types of stromal cells in breast tissue because they all come from a common progenitor cell. The group conclude that GT198 expression is, therefore, a specific marker of mutant breast tumour stroma and has the potential to facilitate diagnosis and targeted treatment of human breast cancer.
The team surmise that their findings suggest multiple lineages of breast tumour stromal cells are mutated in GT198 which imply the presence of mutant progenitors; whereas their descendants, carrying the same GT198 mutations, are collectively responsible for forming breast tumour microenvironment. For the future, the researchers state that the way to treat breast cancer may be to target the progenitor cells. They go to add that these cells which are feeding the tumour should be killed as opposed to just killing the tumour cells, which is less effective.