The Myc protein can cause a lot of trouble when it’s mutated or expressed incorrectly. Under those condition it’s called an oncogene, and it’s associated with the development of more than half of all human cancers. But because its cellular influence is vast (it controls the expression of thousands of genes and regulatory molecules), it’s been tough for scientists to learn which of its many effects are cancer-causing.
Now oncologist Dean Felsher, MD, PhD, and his colleagues have found that just a handful of genes are responsible for the Myc oncogene’s devastating outcomes. Their work was published today in Cancer Cell. As I wrote in our release:
The genes identified by the researchers produce proteins that govern whether a cell self-renews by dividing, enters a resting state called senescence or takes itself permanently out of commission through programmed cell suicide. Exquisite control of these processes is necessary to control or eliminate potentially dangerous tumor cells.
In particular, the researchers found that Myc works through a family of regulatory RNA molecules that govern how (and when) tightly packaged genes in the DNA/protein complex called chromatin are made available for transcription into proteins that do much of the work of the cell. Understanding this process might help researchers find ways to throw a molecular wrench into the Myc mechanism.
“One of the biggest unanswered questions in oncology is how oncogenes cause cancer, and whether you can replace an oncogene with another gene product,” Felsher told me. “These experiments begin to reveal how Myc affects the self-renewal decisions of cells. They may also help us target those aspects of Myc overexpression that contribute to the cancer phenotype.”
The reliance of many cancer cells on oncogenes like Myc is called oncogene addiction. In many cases, blocking the expression of an oncogene, or tinkering with its activity, causes cancer cells to stop growing and tumors in animals to regress. Recently Felsher and his colleagues published an article in the Proceedings of the National Academy of Sciences describing how inactivating two oncogenes at once can work better to fight cancer in animal models by making it more difficult for the cancer cells to develop resistance to therapy.
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