Gene important to breast development, breast cancer identified

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Washington: Scientists have identified a gene important to breast development and breast cancer, a finding that provides a potential new target for drug therapies to treat aggressive forms of the disease.

In breast tissue, there are two main types of cells: luminal cells and 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.

Previous work led by Charlotte Kuperwasser, principal investigator of the study from Tufts University, determined that some common forms of breast cancer originate from luminal cells while some rarer forms of breast cancer originate from basal cells.

In the new study, researchers identified 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 potentially treating certain difficult-to-treat forms of breast cancer.

TAZ helps to regulate how different genes operate in different cell types, researchers said.

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 tumours from women with either luminal or basal tumours.

The research team found 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 tumours.

"We've known for a long time that breast cells can lose their normal identity when they become cancerous, but we are now realising that normal cells can change their characteristics as well in response to transcription factors like TAZ," said first author Adam Skibinski.

"This might be a factor in the development of breast cancer," said Skibinski, a PhD student at Tufts University School of Medicine and the Sackler School of Graduate Biomedical Sciences at Tufts University.


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