They add that because this gene, known as PTPRD, has recently been found to be inactivated in several other cancers as well, their discovery suggests that PTPRD may play a tumor suppressor role in a wide variety of different cancers.
The findings are published in the December 15 issue of Cancer Research.
"Over the past decade several dozen tumor suppressor genes have been identified, but only a minority of them is important in causing many different tumor types. PTPRD seems to be one of these broad spectrum tumor suppressor genes," says the study's lead investigator, Todd Waldman, MD, PhD, an associate professor of oncology at Georgetown's Lombardi Comprehensive Cancer Center.
If the hypothesis is true – and Waldman and his team are now investigating loss of PTPRD in a number of additional cancers – then it may be possible to design a therapy that has wide applicability in oncology, he says.
"Most targeted cancer drugs today work by inhibiting gene products that are overactive in cancer cells. In this case, it is loss of the PTPRD gene that leads to cancer," Waldman says. "Therefore, we are trying to discover the molecules that PTPRD's protein controls, and then we plan to target these downstream molecules with a novel agent."
Waldman found that when the researchers restored production of the gene's protein in cancer cells that harbored PTPRD deletions or mutations, these tumors stopped growing and initiated a program of cell suicide.
The researchers also discovered PTPRD mutations in both the blood and in tumors of a patient with multiple different kinds of cancers. "This suggests that the gene could be responsible for an inherited predisposition to cancer," Waldman says
PTPRD produces a receptor protein tyrosine phosphatase that bisects the outer membrane of a cell. The part that protrudes outside the cell body is thought to be involved in helping cells stick to each other to form a tissue as well as in cell-to-cell communication. The part that juts into the cell is an enzyme that removes phosphates from other proteins – in other words, it changes the activity of proteins either by activating or deactivating them, Waldman says.
"In the absence of PTPRD, there are as yet unknown proteins floating around inside the cell with more phosphate residues than they should have, and it is a well known fact that the presence of these residues activates cellular growth pathways," he says. But it is not yet known which specific proteins PTPRD regulates, Waldman says.
Deletions of PTPRD in human cancer cells were first discovered in 2005, and since then, deletions or mutations of the gene have been discovered in several cancer types, including those of the colon and lung.
In this study, Waldman and his research team, which includes investigators from the National Cancer Institute, the University of Iowa and Duke University, used a laboratory technique known as copy number analysis to look for PTPRD in melanoma cell lines and in samples of human glioblastoma multiforme, the deadliest of brain cancers.
This technique uses a gene microarray that contains millions of probes that can stick to different regions of the human genome. The researchers purified DNA from tumors and then used the microarray chip to quantify genomic copy number. They found that PTPRD was deleted or mutated in 12 percent of melanoma tumors and in 14 percent of glioblastoma tumors examined. "That makes PTPRD one of the most commonly mutated genes discovered yet in melanoma," Waldman says.
"Before this study, no single tyrosine phosphatase was thought to play a generally important role as a tumor suppressor gene n multiple tumor types," Waldman says. "Now we have provided the first functional evidence that PTPRD is a tumor suppressor gene, and potentially an important one at that."
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21.11.2017 | Albert-Ludwigs-Universität Freiburg im Breisgau
The WHO reports an estimated 429,000 malaria deaths each year. The disease mostly affects tropical and subtropical regions and in particular the African continent. The Fraunhofer Institute for Silicate Research ISC teamed up with the Fraunhofer Institute for Molecular Biology and Applied Ecology IME and the Institute of Tropical Medicine at the University of Tübingen for a new test method to detect malaria parasites in blood. The idea of the research project “NanoFRET” is to develop a highly sensitive and reliable rapid diagnostic test so that patient treatment can begin as early as possible.
Malaria is caused by parasites transmitted by mosquito bite. The most dangerous form of malaria is malaria tropica. Left untreated, it is fatal in most cases....
The formation of stars in distant galaxies is still largely unexplored. For the first time, astron-omers at the University of Geneva have now been able to closely observe a star system six billion light-years away. In doing so, they are confirming earlier simulations made by the University of Zurich. One special effect is made possible by the multiple reflections of images that run through the cosmos like a snake.
Today, astronomers have a pretty accurate idea of how stars were formed in the recent cosmic past. But do these laws also apply to older galaxies? For around a...
Just because someone is smart and well-motivated doesn't mean he or she can learn the visual skills needed to excel at tasks like matching fingerprints, interpreting medical X-rays, keeping track of aircraft on radar displays or forensic face matching.
That is the implication of a new study which shows for the first time that there is a broad range of differences in people's visual ability and that these...
Computer Tomography (CT) is a standard procedure in hospitals, but so far, the technology has not been suitable for imaging extremely small objects. In PNAS, a team from the Technical University of Munich (TUM) describes a Nano-CT device that creates three-dimensional x-ray images at resolutions up to 100 nanometers. The first test application: Together with colleagues from the University of Kassel and Helmholtz-Zentrum Geesthacht the researchers analyzed the locomotory system of a velvet worm.
During a CT analysis, the object under investigation is x-rayed and a detector measures the respective amount of radiation absorbed from various angles....
The quantum world is fragile; error correction codes are needed to protect the information stored in a quantum object from the deteriorating effects of noise. Quantum physicists in Innsbruck have developed a protocol to pass quantum information between differently encoded building blocks of a future quantum computer, such as processors and memories. Scientists may use this protocol in the future to build a data bus for quantum computers. The researchers have published their work in the journal Nature Communications.
Future quantum computers will be able to solve problems where conventional computers fail today. We are still far away from any large-scale implementation,...
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21.11.2017 | Physics and Astronomy
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21.11.2017 | Life Sciences