Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Gene used in brain development can cause childhood brain cancers

03.02.2005


Errant neuro-developmental gene responsive to a potent vitamin A derivative



A gene that’s normally silenced after contributing to brain development was found to be expressed in cells from medulloblastoma, the most common form of pediatric brain malignancy in children, scientists report in an article published in the February 1 issue of the journal Cancer Research.

In their study, the scientists discovered that multiple extra copies of the gene, called OTX2, had been switched back on among tumor cells removed from patients with medulloblastoma brain tumors. In the United States, medulloblastoma accounts for approximately 30 percent of all pediatric brain tumors.


Further, the scientists discovered that a potent derivative of Vitamin A, known as all trans-retinoic acid or ATRA, suppressed growth and induced cell death among the OTX2-laden tumor cells. More than half of medulloblastomas grown in the laboratory responded to ATRA treatment.

"The response that ATRA imposes upon these medulloblastoma brain tumor cell lines suggests that this type of tumor may respond favorably to ATRA-based therapy," said Hai Yan, M.D., Ph.D., the principle investigator of the study at the Brain Tumor Center at the Duke University Medical Center.

"ATRA is already clinically approved for the treatment of acute promyelocytic leukemia. These studies lay the conceptual and practical framework for clinical trials using ATRA in the treatment of a commonly lethal pediatric disease."

Yan said that the OTX2 gene normally contributes to development and growth of certain areas of the brain, such as the cerebellum, but the gene is generally turned off and no longer used after birth.

Using a novel technique that involves snipping apart the entire DNA content in the chromosomes of medulloblastoma cells and then analyzing the quantity of each, Yan and his colleagues detected an abnormally amplified segment among the tumor cells on chromosome 14.

"There was a striking amplification of genetic coding representing a 28-fold increase in base pairs of DNA in that specific region of chromosome 14," Yan said. The researchers identified OTX2 as the only gene contained within the amplified region of the chromosome.

The scientists also determined that 60-70 percent of the medulloblastoma cells were churning out large numbers of messenger RNA specific for OTX2, compared to normal cells which generally show no activity for this gene.

This latter finding suggested another approach, RNA interference, to blocking OTX2 activity. Discovered in the late 90’s, RNA interference or RNAi refers to the introduction of double-stranded RNA (dsRNA) into a cell, where it induces the degradation of complementary messenger RNA, thereby suppressing the gene expression.

"In our studies, we applied several specifically designed RNAi to the tumor cells that expressed OTX2," Yan said. "We then observed that the RNAi knocked down OTX2 expression and killed the tumors cells which expressed OTX2. In contrast, the RNAi did not do any damage to the cells which did not express OTX2."

Among the researchers working with Yan to investigate the OTX2 gene in medulloblastomas were, Chunhui Di, Shaoxi Liao M.D, Ph.D, David C. Adamson, M.D., Ph.D., Timothy J. Parrett, M.D., Daniel K. Broderick, Qun Shi, Roger E. McLendon, M.D., and Darell D. Bigner, M.D., Ph.D. from the Brain Tumor Center, Department of Pathology, Duke University Medical Center, Durham, N.C.; Christoph Lengauer, Ph.D., Jordan M. Cummins, and Victor E.Velculescu, M.D., Ph.D. from The Johns Hopkins University Medical Institutions, Baltimore, Md.; and Daniel W. Fults, M.D. from the University of Utah School of Medicine, Salt Lake City, Utah.

Russell Vanderboom, Ph.D. | EurekAlert!
Further information:
http://www.aacr.org

More articles from Life Sciences:

nachricht Ambush in a petri dish
24.11.2017 | Friedrich-Schiller-Universität Jena

nachricht Meadows beat out shrubs when it comes to storing carbon
23.11.2017 | Norwegian University of Science and Technology

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: New proton record: Researchers measure magnetic moment with greatest possible precision

High-precision measurement of the g-factor eleven times more precise than before / Results indicate a strong similarity between protons and antiprotons

The magnetic moment of an individual proton is inconceivably small, but can still be quantified. The basis for undertaking this measurement was laid over ten...

Im Focus: Frictional Heat Powers Hydrothermal Activity on Enceladus

Computer simulation shows how the icy moon heats water in a porous rock core

Heat from the friction of rocks caused by tidal forces could be the “engine” for the hydrothermal activity on Saturn's moon Enceladus. This presupposes that...

Im Focus: Nanoparticles help with malaria diagnosis – new rapid test in development

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....

Im Focus: A “cosmic snake” reveals the structure of remote galaxies

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...

Im Focus: Visual intelligence is not the same as IQ

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...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Ecology Across Borders: International conference brings together 1,500 ecologists

15.11.2017 | Event News

Road into laboratory: Users discuss biaxial fatigue-testing for car and truck wheel

15.11.2017 | Event News

#Berlin5GWeek: The right network for Industry 4.0

30.10.2017 | Event News

 
Latest News

IceCube experiment finds Earth can block high-energy particles from nuclear reactions

24.11.2017 | Physics and Astronomy

A 'half-hearted' solution to one-sided heart failure

24.11.2017 | Health and Medicine

Heidelberg Researchers Study Unique Underwater Stalactites

24.11.2017 | Earth Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>