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Researchers Find How Two Cancer Genes Interact To Cause Malignancy

Date:
February 26, 1999
Source:
Duke University Medical Center
Summary:
Researchers at Duke University Medical Center have discovered how two cancer-causing genes can interact to transform normal cells into cancerous cells, adding further insight into the long-held theory that cancers require mutations in multiple genes.

DURHAM, N.C. -- Researchers at Duke University Medical Center have discovered how two cancer-causing genes can interact to transform normal cells into cancerous cells, adding further insight into the long-held theory that cancers require mutations in multiple genes.

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In a paper published in the Feb. 26 issue of Molecular Cell, geneticist Joseph Nevins and his colleagues report details of the functional interaction between the proteins produced by two cancer-related genes, called "myc" and "ras."

Basically, the researchers discovered that mutated ras causes the protein from myc to accumulate in the cell, enhancing myc's growth-promoting abilities. If ras is not mutated, the myc growth-stimulating signal dies rapidly and cellular replication is controlled.

"The 'multi-hit' notion of cancer has been around for a while," said Nevins, a Howard Hughes Medical Institute Investigator at Duke. "In the mid 1980s scientists showed that if both myc and ras were mutated, the cells became cancerous. Until now there has been little mechanistic information as to how these two genes work together."

The researchers' report shows that the myc protein lasts five times longer than normal if ras is mutated. This information could eventually affect treatment and diagnosis of many cancers, including brain, colorectal and endometrial (uterine). Tumor cells with mutations in both myc and ras are likely to have an even more dramatic increase in the duration of the myc growth signal, Nevins said.

"The key to developing better therapeutics for cancer," said Nevins, "is using the information learned about interactions such as that of ras with myc to design drugs that interfere with these oncogenic processes." Like all so-called oncogenes, myc and ras perform important cell functions when normal, but act as accelerators to spur uncontrolled cell proliferation when mutated. In normal cells, the amount of protein produced by the myc gene increases to promote cell growth and then drops to prevent cells from multiplying further. Ras is important in transmitting signals through the cell.

In their experiments on normal cells, the researchers found that without mutated ras, half of the myc protein initially present was degraded within 10 minutes.

However, in cells with mutated ras, it took 50 minutes to degrade half of the myc protein. Myc protein's half-life is longer because the mutated ras protein interferes with the cell's natural degradation of myc protein, much like clogging a sink. As the myc protein accumulates, the cells continue to divide after they should have stopped.

"The myc protein is normally very short-lived, but a mutated ras can increase its stability," Nevins explained. "This is probably not the only way these two proteins and genes interact, but it is one way."

The researchers still are exploring the exact mechanism by which ras protein interferes with myc's degradation, as well as seeking other factors in the cell that control the stability of myc. More detailed knowledge could lead to new therapies, Nevins said.

"Understanding the precise mechanisms that regulate these activities opens the way to developing therapeutics that specifically target the abnormal function, leaving the normal functions alone," he said.

Other authors of the Molecular Cell study were Rosalie Sears and Gustavo Leone of Duke, and James DiGregori, formerly of Duke and now at the University of Colorado at Denver.


Story Source:

The above story is based on materials provided by Duke University Medical Center. Note: Materials may be edited for content and length.


Cite This Page:

Duke University Medical Center. "Researchers Find How Two Cancer Genes Interact To Cause Malignancy." ScienceDaily. ScienceDaily, 26 February 1999. <www.sciencedaily.com/releases/1999/02/990226081253.htm>.
Duke University Medical Center. (1999, February 26). Researchers Find How Two Cancer Genes Interact To Cause Malignancy. ScienceDaily. Retrieved October 31, 2014 from www.sciencedaily.com/releases/1999/02/990226081253.htm
Duke University Medical Center. "Researchers Find How Two Cancer Genes Interact To Cause Malignancy." ScienceDaily. www.sciencedaily.com/releases/1999/02/990226081253.htm (accessed October 31, 2014).

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