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UNC-CH Researchers Discover Key Cancer Control Mechanism

NEWS By DAVID WILLIAMSON
UNC-CH News Services

CHAPEL HILL -- A gene called ARF attaches to and disables a protein known as MDM2 and in the process helps protect the body against cancer, University of North Carolina at Chapel Hill School of Medicine researchers have discovered.

The mechanism appears to be one of the most potent natural ways of fighting tumor development, the scientists say. After more research, it might be manipulated to treat cancer more successfully or detect it earlier.

"While this work is not a cure for cancer, it is very important for several reasons," said Dr. Yue Xiong, assistant professor of biochemistry at the UNC Lineberger Comprehensive Cancer Center. "First, it provides a mechanism by which ARF suppresses tumor growth. It also may explain why a certain genetic locus, or site on a chromosome, is frequently missing in human cancer." A report on the discovery appears in the current (March 20) issue of Cell, a scientific journal. Besides Xiong (pronounced "Jong"), authors are Dr. Yanping Zhang, a postdoctoral fellow at the Lineberger center, and Dr. Wendell G. Yarbrough, assistant professor of surgery.

In human cancers, a gene known as P53 is mutated in about 50 percent of cases, Xiong said. The ARF gene is missing in about 40 percent.

"When activated, both these genes suppress tumors. When they are absent or damaged, we have a much greater chance of developing tumors," he said.

Soon after the body detects damage to DNA that might lead to cancer, normally low levels of P53 skyrocket and halt cell proliferation similar to how a fire extinguisher smothers a blaze, Xiong said. Healthy cells keep P53 in check when it is not needed by degrading it with the MDM2 protein.

"When DNA is damaged, MDM2 must be decreased to allow the protective P53 to increase
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Contact: David L. Williamson
rdtokids@email.unc.edu
919-962-8596
University of North Carolina at Chapel Hill
22-Mar-1998


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