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.
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
Contact: Joanna Downer
Duke University Medical Center