Discovery of Gene Mechanism may Lead to Developments in Breast Cancer Treatment

Scientists have discovered the mechanism by which a gene that is crucial to the spread of breast cancer is turned on and off.

Robert H. Singer, PhD, professor, co-chair of anatomy and structural biology, and co-director of the Gruss-Lipper Biophotonics Center, Albert Einstein College of Medicine,Yeshiva University, and colleagues discovered that the zipcode binding protein 1 (ZBP1) gene is silenced “when a methyl group (CH3) attaches to ZBP1's promoter region.” The joining of the methyl group inhibits the ability of the promoter to bind to the protein beta-catenin. Without the protein, “the ZBP1 gene is effectively silenced,” according to the researchers.

An additional finding of the study was that when ZBP1 is silenced, cancer cells are better able to migrate, promoting an increase in metastatic cells.

The new finding builds on Singer’s discovery of the ZBP1 gene several years ago. In that research, Singer discovered that the gene helps cells “move, grow, and organize spatially.” Since then, researchers have found that the gene is reactivated in some cancers, including breast, colorectal, and non-small cell lung cancers, but is silenced when cancer cells have metastasized.

According to the researchers, the new discovery may lead to the ability to predict whether a breast tumor is likely to spread, in turn aiding oncologists in choosing a course of treatment, and possibly leading to the development of new targets in treatment.

"If you could turn on this protein in cancer cells, or prevent it from being turned off, you could seriously reduce the ability of the cells to metastasize," said Singer.

A next step for the researchers is analyzing if the ZBP1 gene in cancer cells can be reactivated and the cells “prevented from metastasizing” if CH3 is selectively removed from the promoter.

Findings of the study will be published in the May 20 online edition of the Journal of Cell Science

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