ERα-dicating the Core of Breast Cancer Resistance


Scientists have made an important breakthrough in understanding a key player in most breast cancers. At The Institute of Cancer Research in London, a team has found a new way to look at certain proteins that play a big part in how breast cancer develops.

By focusing on a specific protein that’s found in about 70% of breast cancer cases, they’ve not only got a better grip on how this protein works but also spotted some new targets that could help in creating better treatments.

Breast cancer, particularly the type that is positive for estrogen receptor alpha (ERα), which represents about nearly seventy percent of cases, is influenced significantly by estrogen.

ERα, when activated by estrogen, moves to the nucleus of a cancer cell and interacts with various proteins to promote cancer cell proliferation and survival. Previous treatments have aimed at preventing ERα from binding to estrogen, but cancers often develop resistance to these therapies.

This resistance is thought to be due in part to abnormal interactions between ERα and surrounding proteins.

To tackle this issue, the research team employed a novel technique for studying protein interactions called biotinylation by antibody recognition (BAR).

This method uses antibodies coupled with enzymes to specifically target proteins of interest for study, avoiding the need for genetically altering the cells. The technique involves tagging proteins with a specific amino acid sequence (an epitope) recognized by a targeted antibody, followed by a secondary antibody that attaches biotin to nearby proteins.

This method allows for the identification of proteins interacting with ERα, including those previously unknown.

By utilizing mass spectrometry, the researchers identified 329 proteins known to interact with ERα and discovered 22 new ones. These findings help narrow down proteins that could be involved in developing resistance to breast cancer treatments and highlight 97 proteins for further study.

This approach not only sheds light on the complex interactions between ERα and other proteins within cells but also paves the way for exploring potential new therapeutic targets for ERα-positive breast cancer.

The successful application of BAR could lead to a better understanding of treatment resistance mechanisms and the development of more effective targeted therapies.

Additionally, this method has potential applications beyond breast cancer, offering new opportunities to study protein interactions in various diseases influenced by estrogen signaling and other types of cancer.

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