Gene found that is essential to maintaining breast and cancer cells

The gene and hormone soup that enables women to breastfeed their newborns also can be a recipe for breast cancer, particularly when the first pregnancy is after age 30.

 

Researchers have now found that the gene DNMT1 is essential to maintaining breast, or mammary,  stem cells, that enable normal rapid growth of the breasts during pregnancy, as well as the cancer stem cells that may enable breast cancer. They’ve learned that the DNMT1 gene also is highly expressed in the most common types of breast cancer.

 

Conversely, ISL1 gene, a tumour suppressor and natural control mechanism for stem cells, is nearly silent in the breasts during pregnancy as well as cancer, said Dr. Muthusamy Thangaraju, biochemist at the Medical College of Georgia at Georgia Regents University.

 

“DNMT1 directly regulates ISL1,” Thangaraju said. “If the DNMT1 expression is high, this ISL1 gene is low.” They first made the connection when they knocked out DNMT1 in a mouse and noted the increase in ISL1. Then they got busy looking at what happened in human breast cancer cells.

 

They found ISL1 is silent in most human breast cancers and that restoring higher levels to the human breast cancer cells dramatically reduces the stem cell populations and the resulting cell growth and spread that are hallmarks of cancer.

 

When they eliminated the DNMT1 gene in a breast-cancer mouse model, “The breast won’t develop as well,” Thangaraju said, but neither would about 80 percent of breast tumours. The deletion even impacted super-aggressive, triple-negative breast cancer.

 

The findings point toward new therapeutic targets for breast cancer and potentially using blood levels of ISL1 as a way to diagnose early breast cancer, the researchers report. In fact, they’ve found that the anti-seizure medication valproic acid, already used in combination with chemotherapy to treat breast cancer, appears to increase ISL1 expression, which may help explain why the drug works for these patients, he said. The scientists are screening other small molecules that might work as well or better.

Georgia Regents University and Health System