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 to changes in protein levels of a key gene that is essential for normal distribution of genetic material between daughter cells during cell division."
The findings are a positive step, he emphasizes, because they suggest that halting Myc's action on protein production with targeted therapies could prevent harmful genetic changes in cells that lead to cancer progressi
|Contact: Kirsten Michener|
University of California - San Francisco