Switch Mechanism Found to Stop Cancer Spread

In the studies, which were published in the September 7-11, 2009, issue of Proceedings of the [U.S.] National Academy of Sciences (PNAS), Dr. Alan Garen, from the department of molecular biophysics and biochemistry at Yale University (New Haven, CT, USA) and his colleague Dr. Xu Song, from Sichuan University (Chengdu, China), clarify how cancer may overcome an organism's natural "stop sign” for cell division. During early development, stem cells give rise to other cells that differentiate into all types of tissue. New cell division and proliferation stop as the organism matures. However, cancer can takeover this process and trigger the uncontrolled cell division that produces cancer tumors.

One process that stops cell proliferation is a family of tumor-suppressor proteins (TSPs) that bind to and block the function of protooncogenes, the genes that have the potential to initiate cancer. Dr. Garen's team, working with lab mice, discovered that an RNA molecule from a region of the genome that does not produce proteins prevents a type of TSP from inactivating these incipient cancer genes. The TSP protein they researched, called PSF, is practically identical in mice and humans, according to Dr. Garen.

The Yale team succeeded in preventing the formation of tumors in mice by either increasing the amount of PSF or decreasing the amount of the noncoding RNA in a cell. "The tumor cell stops proliferating and the tumor regresses in a mouse model of cancer, suggesting that both procedures could be the basis of a clinical protocol,” said Dr. Garen, who is a member of Yale Cancer Center.

Dr. Garen and his colleagues plan to continue their research on the mechanism that regulates the amount of PSF-binding RNA in a cell, which they believe is key to the origins of cancer.

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