Stanford University School of Medicine researchers found that switching off a single malfunctioning gene, c-Myc, which produces a protein that promotes cell division, not only stopped uncontrolled cell division but also reactivated senescence in mice.
“What was unexpected was just the fact that cancer cells had retained the ability to undergo senescence at all,” says Dean Felsher, M.D., Ph.D., associate professor of medicine and pathology. Researchers have long thought the senescence process had to be irreversibly disrupted for a tumor to develop.
Although Dr. Felsher's lab had previously shown that mouse tumors diminished and disappeared when Myc was switched off, they hadn't been sure how the process actually worked.
The researchers worked with a series of mice engineered to have Myc-triggered cancers of either the liver, blood, or bones along with a specially constructed version of the Myc gene that they could switch off by feeding the mice antibiotics.
While looking at enzymes associated with the senescence process as well as some molecular markers the sceintists confirmed their suspicion that the sudden diminishing of tumors might be due to the reactivation of some latent remnant of the trigger for senescence. Not only was senescence occurring in cells that had been thought to be incapable of it, the process was reactivated in all the different tumors they studied, including lymphoma, osteosarcoma, and hepatocellular carcinoma.
The study is published July 30 in the advance online version of the Proceedings of the National Academy of Sciences.