Loss of ER expression in approximately one-quarter of recurrent estrogen receptor-positive (ER+) breast cancers makes them immune to endocrine therapy and able to spread uncontrollably.
A recent study published in the Proceedings of the National Academy of Sciences by a group of researchers at Baylor College of Medicine reveals a mechanism that not only explains the process but also suggests solutions to stop it.
“For years, our goal has been to unravel the complex puzzle of breast cancer progression to understand how players interact with each other to provide resistance to therapy and continued development,” said corresponding author Dr. Wei. -Chin Lin, Professor of Medicine- Hematology and Oncology and Molecular and Cellular Biology in Baylor. “Our goal is to overcome this barrier to restore ER receptor expression in these cancers so that they become more susceptible to re-therapy, giving patients a better chance of recovery.”
How breast cancer cells make their ER . loses
Breast cancer resistance to endocrine therapy has previously been linked to two cellular proteins known as 14-3-3 and ER-36.
“Working with a mouse model of human ER+ breast cancer, we were surprised to find that overexpressing 14-3-3t in these tumors caused all cancer cells to become ER-negative (ER-),” Lin Said Dr., a member of the Dan L. Duncan Comprehensive Cancer Center. “I still remember the day I looked at the data. The change was dramatic—all the tumors had lost their ER!”
Studying the mechanism in animal models would be laborious, time-consuming and costly, so the researchers developed an alternative model. First author Lidija A. of Baylor’s Cancer and Cell Biology Graduate Program working in the Linn lab. Wilhelm Garen developed a spheroid model of human breast cancer cells that mimics the progression from ER+ to ER- and provides a handy experimental tool for the future. investigation.
“In a patient, a mammary tumor can take years to grow from ER+ to ER-, in our animal model it takes several months but in our spheroid model it changes from ER+ to ER- in 1 to 2 weeks ,” Garan said.
In the lab spheroid model, the team found that once 14-3-3t is over-expressed in cancer cells under the right conditions, the cells will increase their ERa36 levels followed by loss of the ER.
“Other molecular players, such as AKT and GATA3, are also needed,” Garan said. “Importantly, we also found that factors produced by the tumor microenvironment, which includes fibroblasts and immune cells that are part of the tumor mass and cross-talk with cancer cells, are also required for the progression from ER+ to ER-. “
“We knew that 14-3-3t, ERa36, AKT and GATA3 were key players in the conversion of ER+ breast cancer cells to ER- cells. Here we determined how they functionally interact with each other, Prepare a road map. ER leads to damage,” Lin said. “I am very excited that with our spheroidal breast cancer model we now have the opportunity to test drugs not only to study the cellular changes involved in breast cancer progression but also for their ability to inhibit the process that leads to ER loss. A valuable tool to have.”
“The protein 14-3-3t is overexpressed in about 60% of breast cancers. Not all patients with high 14-3-3t will lose the ER, but for those who do, our findings may one day help shed their tumors.” Medical-sensitive states,” Garan said. “The translational aspect of this research has always been close to my heart – to bring discoveries to the clinic and improve people’s lives.”
This story has been published without modification in text from a wire agency feed.
catch all business News, market news, today’s fresh news events and breaking news Updates on Live Mint. download mint news app To get daily market updates.