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Cancer-Causing Gene Discovery Suggests New Therapies
Date:1/23/2009

how the oncogene affected the subsequent production of proteins, a step known as translation, was unknown.

"A cancer causing gene, such as Myc, regulates many distinct cellular processes, and that can make it very difficult to tease apart which ones are the most important for the cancer to progress," says Barna, a faculty fellow in the UCSF biochemistry and biophysics department. "The key to our studies was the ability to generate novel genetic tools to halt Myc's action on protein production. This demonstrates how essential this process is for cancer formation."

To test whether protein production induced by Myc played a role in cancer, the UCSF- led team genetically crossed two types of mice: one that was cancer-prone and overexpressed the Myc oncogene and one that was newly engineered to lower protein production. The new cross of mice possessed not only the well-known destructive Myc traits, but also an enhanced ability to damp down protein production.

In these mice, the restrained protein production restored to near-normal the cell growth, division and protective cell-sacrifice needed to counter cancer.

The scientists also found that this increased control over the so-called "translation" of RNA into proteins countered damage to chromosome function otherwise caused by Myc, and preserved functions vital to faithful cell division. Changes in the genetic integrity of cells are recognized as hallmarks of cancer, and the new findings show that Myc can cause these abnormalities through control of protein production.

The research suggests that Myc may disrupt a number of genes "downstream" of its damage to DNA, the scientists say.

"We discovered a previously unrecognized link between alterations in protein synthesis and the mechanism by which cells maintain the integrity of the genome," Ruggero stresses. "We found that when Myc is overexpressed, this leads
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