Researchers link new molecular culprit to breast cancer progression

Johns Hopkins researchers have uncovered a protein ''partner'' commonly used by breast cancer cells to unlock genes needed for spreading the disease around the body. A report on the discovery, published 5 November on the website of the Proceedings of the National Academy of Sciences, details how some tumours get the tools they need to metastasize.

''We've identified a protein that wasn't known before to be involved in breast cancer progression,'' says Gregg Semenza, MD, PhD., the C Michael Armstrong Professor of Medicine at the Johns Hopkins University School of Medicine and director of the Vascular Program at Hopkins' Institute for Cell Engineering.

''The protein JMJD2C is the key that opens up a whole suite of genes needed for tumors to grow and metastasize, so it represents a potential target for cancer drug development,'' adds Semenza.

Semenza and his colleagues made their finding when they traced the activity of HIF-1, a protein known to switch on hundreds of genes involved in development, red blood cell production, and metabolism in normal cells. Previous studies had shown that HIF-1 could also be hijacked to switch on genes needed to make breast tumors more malignant.

Would-be tumour cells face a host of challenges as they make the transition from working with their host to working against it, such as the need to evade the immune system and to produce more cancer cells, explains Weibo Luo, Ph.D., an instructor in the Institute for Cell Engineering and Department of Biological Chemistry who led the project. All of these efforts require switching on the right genes for the job.

To learn more about how HIF-1 works, the researchers tested a range of human proteins to see whether they would interact with HIF-1. They then sifted through the 200 resulting hits, looking for proteins involved in chemical changes to sections of DNA that determine whether or not the genes they contain are available for use. ''In order for HIF-1 to switch genes on, they have to be available, but many of the genes HIF-1 activates are normally locked down in mature cells,'' explains Luo. ''So we thought HIF-1 must have a partner that can do the unlocking.''