“We took a new approach to a 50-year-old debate about whether people with Down syndrome develop cancer less often than other people,” says Roger H. Reeves, Ph.D., professor of physiology in the McKusick-Nathans Institute of Genetic Medicine at Hopkins. “Studying the genetic differences associated with Down syndrome has revealed a new way of thinking about repressing cancer growth in everyone.”
The research team started with a mouse model that carries, rather than a whole extra copy of chromosome 21 as is seen in trisomy 21, or Down syndrome, a partial copy containing 108 genes. They then mated those trisomic mice to mice that carry a mutation that causes intestinal tumors, similar to those seen in colon cancer in humans. The trisomic, colon cancer mice had 44 percent fewer intestinal tumors compared to the colon cancer mice without the extra 108 genes.
The team then used another mouse model of Down syndrome, one that carries extra copies of only 33 of the genes on chromosome 21, and repeated their genetic crosses. Mice with three copies of the 33 genes developed half the number of tumors as mice with the standard two copies. Mice carrying a deletion that left them with only one copy of these 33 genes developed twice the number of tumors as usual.
“Not only does having an extra copy of one or more of these genes repress tumor formation, it turns out that missing a copy enhances tumor growth-this was really surprising,” says Reeves.
Taking a closer look at the 33 genes to identify a likely culprit for the dose-specific relationship with tumor growth, the researchers focused on one gene, Ets2, which previously has been implicated as a cause of cancer. However, some research suggested that Ets2 activity might be involved in pathways that cause cells to die.
They then repeated their genetic crosses, this time with mice that had three, two or one copy of the Ets2 gene only. Once again, mice that were trisomic for 33 genes (including Ets2) had fewer tumors, but mice that were trisomic for 32 of these genes but had the normal two copies of Ets2 had a tumor number similar to control (non-trisomic) mice. Mice with just one copy of Ets2 developed more tumors.
“These results support studies concluding that people with Down syndrome get fewer cancers of many types. While we’ve only shown this effect with Ets2 and a particular type of colon tumor in mice, we think that the human Ets2 gene might contribute to resistance toward other types of cancer, based on what happens in Down syndrome,” says Reeves.
“Our findings are significant because they broaden the definition of an ‘oncogene’ or ‘tumor suppressor gene’ to include the effect of gene dosage,” says Michael Ostrowski, an Ohio State cancer researcher and Ets2 expert who developed the mouse models used in this study. “They also suggest that finding ways to increase the expression of genes such as Ets2 might lead to a new strategy for treating or controlling cancer,” he says.
Audrey Huang | EurekAlert!
Multi-institutional collaboration uncovers how molecular machines assemble
02.12.2016 | Salk Institute
Fertilized egg cells trigger and monitor loss of sperm’s epigenetic memory
02.12.2016 | IMBA - Institut für Molekulare Biotechnologie der Österreichischen Akademie der Wissenschaften GmbH
A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.
Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...
In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.
“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...
The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.
The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...
Broadband rotational spectroscopy unravels structural reshaping of isolated molecules in the gas phase to accommodate water
In two recent publications in the Journal of Chemical Physics and in the Journal of Physical Chemistry Letters, researchers around Melanie Schnell from the Max...
The efficiency of power electronic systems is not solely dependent on electrical efficiency but also on weight, for example, in mobile systems. When the weight of relevant components and devices in airplanes, for instance, is reduced, fuel savings can be achieved and correspondingly greenhouse gas emissions decreased. New materials and components based on gallium nitride (GaN) can help to reduce weight and increase the efficiency. With these new materials, power electronic switches can be operated at higher switching frequency, resulting in higher power density and lower material costs.
Researchers at the Fraunhofer Institute for Solar Energy Systems ISE together with partners have investigated how these materials can be used to make power...
16.11.2016 | Event News
01.11.2016 | Event News
14.10.2016 | Event News
02.12.2016 | Medical Engineering
02.12.2016 | Agricultural and Forestry Science
02.12.2016 | Physics and Astronomy