It has been known for some time that mutations in the APC gene occur in more than 85 percent of all sporadic colon cancers. Now researchers at Huntsman Cancer Institute at the University of Utah demonstrate in a study featured today in Cell the mechanism by which mutation of the APC gene affects a cellular process known as DNA methylation. DNA methylation is a chemical modification made to DNA that plays an important role in dictating how DNA is read and interpreted by a cell.
The group, led by David Jones, Ph.D., and Bradley Cairns, Ph.D., have now linked loss of Apc with DNA demethylase, an enzyme system that erases DNA methylation. Studies using human tissues and zebarafish demonstrate that this system is highly active in tissues harboring mutated Apc and may provide an explanation for the previously known loss of DNA methylation seen in early stage tumors. The activity of the DNA demethylase appears to stall the normal development of intestinal cells, leaving them in a stem cell-like state. Normal development was restored upon inhibition of the DNA demethylase system. The experiments conducted by the group also demonstrated that the mechanistic connection between APC mutation and demethylation is conveyed through changes in the amount of retinoic acid (RA), an important regulatory compound derived from dietary vitamin A.
"We believe that clarification of the mechanism leading to demethylation will have broad implications for a variety of cancers. Our increased understanding of the mechanics connecting APC mutation and demethylation presents new opportunities for colon cancer intervention and may lead the way to developing a truly finely tuned approach to treatment," said Jones. Cairns added, "Since the mechanism of action of the demethylase can inherently create new mutations, misregulation of the system could underlie the occurrence of mutations in additional oncogenes. Its inhibition may therefore allow us to both prevent and treat certain cancers."
The mission of Huntsman Cancer Institute (HCI) at The University of Utah is to understand cancer from its beginnings, to use that knowledge in the creation and improvement of cancer treatments, to relieve the suffering of cancer patients, and to provide education about cancer risk, prevention, and care. HCI is a National Cancer Institute-Designated Cancer Center, which means that it meets the highest national standards for cancer care and research and receives support for its scientific endeavors. HCI is also a member of the National Comprehensive Cancer Network (NCCN), a not-for-profit alliance of the world's leading cancer centers that is dedicated to improving the quality and effectiveness of care provided to patients with cancer. For more information about HCI, please visit www.huntsmancancer.org.
Linda Aagard | EurekAlert!
How brains surrender to sleep
23.06.2017 | IMP - Forschungsinstitut für Molekulare Pathologie GmbH
A new technique isolates neuronal activity during memory consolidation
22.06.2017 | Spanish National Research Council (CSIC)
An international team of scientists has proposed a new multi-disciplinary approach in which an array of new technologies will allow us to map biodiversity and the risks that wildlife is facing at the scale of whole landscapes. The findings are published in Nature Ecology and Evolution. This international research is led by the Kunming Institute of Zoology from China, University of East Anglia, University of Leicester and the Leibniz Institute for Zoo and Wildlife Research.
Using a combination of satellite and ground data, the team proposes that it is now possible to map biodiversity with an accuracy that has not been previously...
Heatwaves in the Arctic, longer periods of vegetation in Europe, severe floods in West Africa – starting in 2021, scientists want to explore the emissions of the greenhouse gas methane with the German-French satellite MERLIN. This is made possible by a new robust laser system of the Fraunhofer Institute for Laser Technology ILT in Aachen, which achieves unprecedented measurement accuracy.
Methane is primarily the result of the decomposition of organic matter. The gas has a 25 times greater warming potential than carbon dioxide, but is not as...
Hydrogen is regarded as the energy source of the future: It is produced with solar power and can be used to generate heat and electricity in fuel cells. Empa researchers have now succeeded in decoding the movement of hydrogen ions in crystals – a key step towards more efficient energy conversion in the hydrogen industry of tomorrow.
As charge carriers, electrons and ions play the leading role in electrochemical energy storage devices and converters such as batteries and fuel cells. Proton...
Scientists from the Excellence Cluster Universe at the Ludwig-Maximilians-Universität Munich have establised "Cosmowebportal", a unique data centre for cosmological simulations located at the Leibniz Supercomputing Centre (LRZ) of the Bavarian Academy of Sciences. The complete results of a series of large hydrodynamical cosmological simulations are available, with data volumes typically exceeding several hundred terabytes. Scientists worldwide can interactively explore these complex simulations via a web interface and directly access the results.
With current telescopes, scientists can observe our Universe’s galaxies and galaxy clusters and their distribution along an invisible cosmic web. From the...
Temperature measurements possible even on the smallest scale / Molecular ruby for use in material sciences, biology, and medicine
Chemists at Johannes Gutenberg University Mainz (JGU) in cooperation with researchers of the German Federal Institute for Materials Research and Testing (BAM)...
19.06.2017 | Event News
13.06.2017 | Event News
13.06.2017 | Event News
23.06.2017 | Physics and Astronomy
23.06.2017 | Physics and Astronomy
23.06.2017 | Information Technology