Important Gene in Development of Breast Cancer Identified

Scientists have identified a gene, which helps to regulate how different genes operate in different cell types. This finding may now allow scientists to utilize new ways to target and treat aggressive types of breast cancer.

In breast cancer, normal cells can become unpredictable or aggressive and thus difficult to treat with anti-cancer drugs. Previous work, determined that some common forms of breast cancer originate from luminal cells while some rarer forms of breast cancer originate from basal cells. Normally luminal cells are "programmed" by a particular class of proteins (transcription factors), which prevent them from becoming basal cells, and vice-versa.

Scientists have pinpointed a gene, TAZ, which controls whether breast cells behave more like basal cells or more like luminal cells, information that might be important in understanding and possibly treating difficult-to-treat forms of breast cancer.

The research team identified TAZ by testing the function of more than 1,000 genes to determine which were involved in "reprogramming" luminal and basal cells, therefore reversing lineage commitment.

To further identify the role of TAZ, the research team studied breast tissue at different stages of development using two groups of mice: a control group with the TAZ gene and an experimental group of knock-out mice with the TAZ gene deleted. The team also looked at the levels of the TAZ gene in tumors from women with either luminal or basal tumors.

The findings, published in Cell Reports, showed that the experimental group had an imbalance of cell populations in breast tissue; too many luminal and too few basal. The control group had a normal ratio of luminal to basal cells. In breast tissue from women with cancer, they found high levels of TAZ in basal but not luminal tumors.

"We've known for a long time that breast cells can lose their normal identity when they become cancerous, but we are now realizing that normal cells can change their characteristics as well in response to transcription factors like TAZ. This might be a factor in the development of breast cancer," said Adam Skibinski, an M.D./Ph.D. student at Tufts University School of Medicine and the Sackler School of Graduate Biomedical Sciences.

Understanding more about how the different types of cells in breast tissue develop improves knowledge of breast cancer. By identifying the genes responsible for this change in cells from breast tissue, researchers now hope to identify a way to stop or reverse it.