Fifteen percent of Americans work the night shift. This boosts the chances of developing cancer, according to studies of cancer risk factors. Biologists at MIT have now found a link that explains this amplifying risk.
In humans and other organisms, a circadian clock is regulated by light. This manages the timing of key aspects of human physiology, by regulating cellular activities.
Conducting a study on mice, MIT researchers found that the same genes that dictate cells’ circadian rhythms also function as tumor suppressors. The disruption of the normal light/dark cycle or gene deletion, causes these tumors to become more aggressive, through loss of suppressors.
Bmal1 is a gene responsible for turning on other genes such as Per2, that control circadian activities, within cells. Proteins encoded by these genes normally oscillate throughout the day, but when normal light/dark cycles are disrupted, those oscillations vanish.
According to an assistant professor of pathology at New York University School of Medicine, “Cells need the light cue, which is like a reset button for the clock. When you lose that cue, you lose the normal rhythms in every cell in your body,”.
Mice that are genetically engineered to develop a type of lung cancer, were tested by the team at NYU School of Medicine to investigate a possible link between cancer and these genes.
These mice were exposed to two different schedules. The first group of mice lived with a normal schedule. They were exposed to 12 hours of light followed by 12 hours of darkness. The other group of mice were exposed to an additional eight hours of light every few days (“jet lag” schedule). When humans travel through multiple time zones or work night shifts, there is a biological clock disruption that occur. The"jet lag" schedule caricatured this disruption.
Tumors were more aggressive and grew faster under the jet lag scenario, than those in the mice living with a normal light/dark schedule.
Researchers conducted a next set of experiments where they got rid of the genes for Bmal1 and Per 2, but kept the mice on a normal light/dark schedule. Just as they did under the jet lag scenario, tumors continued to grow fast.
The chair of the Department of Neuroscience at the University of Texas Southwestern Medical Center, Joseph Takahashi, says the study offers an important link between the circadian clock dysfunction and cancer. Although not involved in the research he also states, "this work is very clear and definitive. That's we need to really show that the circadian clock may have implications for cancer and tumor progression.”
The assistant professor of pathology at New York University School of Medicine plans to study how circadian disruptions affect other types of cancers, and is now researching whether cancer cells that have a broken clock, have any weaknesses that could be exploited.
This research was funded by a National Cancer Institute Cancer Center Support Core Grant, the Lung Cancer Research Foundation, and the Koch Institute Frontier Fund. To learn more contact IPPrecise.