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Scientists show how RET gene in breast cancer cells responds to estrogen

June 14, 2017

"Those two sequences clearly are genetic hubs for the dialing up and dialing down of RET activity in response to estrogen," says Andrew McCallion, Ph.D., an associate professor in the McKusick-Nathans Institute of Genetic Medicine, and corresponding author on the study.

In a second experiment, the team used the cloned sequence and luciferase concoction, inserted it into a breast cancer gene, and this time added retinoic acid instead of estrogen. Retinoic acid is well known to slow cancer cell growth. The scientists showed that one of the two sequences previously shown to be estrogen responsive also responded to retinoic acid and increased RET activity.

The investigators also found that when they put estrogen and retinoic acid together in breast cancer cells in culture, the increased activity of RET was much greater compared to either estrogen or retinoic acid alone.

Because it appears that increased RET activity is linked to more aggressive and tamoxifen-resistant types of breast cancers, the discovery is potentially important for making decisions about tamoxifen use, McCallion says. Understanding the genetics of these proteins also has the potential to guide the search for new therapeutic targets in breast cancer. With the new information, he says, steps might be taken to "resensitize" tumors that become tamoxifin- insensitive by manipulating the regulators of RET and, therefore, its protein products.

Source: Johns Hopkins Medical Institutions