New targets for potential intervention found in the breast cancer

New targets for potential intervention found in the breast cancer -

new scientific targets of Florida campus of The Scripps Research Institute (TSRI) found for potential intervention in breast cancer. These new targets could possibly increase efficiency and reduce undesirable side effects associated with current treatments.

The study was published online before print June 5, 2014 in the journal Structure .

Approximately two out of three breast cancers are driven by receptors that bind estrogen and progesterone hormones when the hormones bind to these receptors in cancer cells, they report the cancer cells to grow. What makes it interesting therapeutic progesterone receptor is that it has two fields AF1 and AF2 activation. Normally both are necessary for the full activation of the receptor.

"Using technology exchange hydrogen-deuterium, our study highlights how AF2 AF1-point communicates with the first evidence of long-term interaction between these two functional areas," said Patrick R. Griffin, professor IRST who led the study. "These results support further research to find promising small molecules that block this interaction."

the results are particularly important because in some mutations AF2 is removed, but the receiver always pushes cancer using the AF1 domain. current drugs used for the treatment of these cancers targeting domain AF2, so with nothing to bind to, they do not work at all. Although several studies have shown the importance of the AF1, the binding domain is remarkably dynamic, frequently changing shape and making it difficult to target with drugs.

in the new study, the scientists used a advanced technology called the hydrogen deuterium exchange mass spectrometry (HDX) to measure the complex interactions between the AF1 and AF2 areas of the progesterone receptor.

HDX mass spectrometry is a high precision, high sensitivity mapping technology that allowed scientists to determine the specific receptor regions that are altered upon interaction. This information was used to infer structural changes that result from the interaction and to probe conformational flexibility intact multidomain proteins.

In addition to exploring potential new drugs for breast cancer, the researchers also hope to study the implications for prostate cancer, other hormone-driven disease.

"many androgen receptor characteristics are similar to the progesterone receptor, as they belong to the same subfamily of steroid receptors," said Devrishi Goswami, the first author of the study and a member of the Griffin lab. "This might work the same way. So these new ideas can also help find new approaches for the treatment of prostate cancer hormone refractory to treatment. "