Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Researchers identify gene that spurs deadly brain cancer

07.12.2009
Howard Hughes Medical Institute (HHMI) researchers have identified a new factor that is necessary for the development of many forms of medulloblastoma, the most common type of malignant childhood brain cancer.

HHMI investigator Huda Y. Zoghbi and colleagues at Baylor College of Medicine prevented medulloblastoma from developing in mice by shutting down production of the protein Atoh1 in susceptible brain cells. The team's findings, reported in the December 4, 2009, issue of Science, suggest Atoh1 may be a new target for medulloblastoma treatment.

"When we cloned the gene for Atoh1 in 1996, we had no clue that it had any medical relevance," said Zoghbi, a neuroscientist and neurologist. "Now we know that it's critical for many medical issues, the most recent one being this common childhood cancer."

Atoh1 (also known as Math1) is a transcription factor that works in the nuclei of cells to keep certain genes switched on. It is evolutionarily ancient, appearing in slightly varying forms in various species, from fruit flies to humans. In cells where Atoh1 is active, it seems to be switched on only during fetal development, when cells proliferate rapidly to fill out the various parts of the nervous system.

However, in the region of the brain known as the cerebellum, Atoh1 is active after birth in the fast-dividing granule neuron precursor (GNPs) cells that eventually stop dividing and become mature granule neurons. "The cerebellar granule neurons are unique in that most of their development happens after birth, both in mice and humans," Zoghbi said.

A few years ago, experiments done in several laboratories hinted that Atoh1 might be required to keep GNPs in their fast-dividing state and make them more susceptible to developing into medulloblastoma tumors.

"The question for us was whether we could really prove, not just in the cell culture dish or in microarrays but in animals, that Atoh1 plays this role in medulloblastoma," Zoghbi said.

Ordinarily, to begin to discern the function of a gene such as Atoh1, researchers would engineer a strain of mice that lack the gene. But that had been tried in the 1990s, and the results were less than satisfying. Researchers found that Atoh1-knockout mice failed to develop properly in the womb, and died at birth. To study Atoh1's function after birth, Zoghbi's team, led by postdoctoral researcher Adriano Flora, devised a more advanced technique. First they bred a strain of mice with a genetic off-switch connected to their Atoh1 gene; then they injected a chemical into the brains of healthy newborn mice, to trigger this off-switch and eliminate the production of Atoh1 in GNPs. As a result, the GNPs immediately stopped proliferating and started maturing into granule neurons.

That result showed that Atoh1 helped keep GNPs in their ever-dividing state. Further experiments revealed that Atoh1 revs up GNPs by switching on a gene called Gli2, a well-known member of the Sonic Hedgehog signaling pathway that helps cells divide. The Sonic Hedgehog pathway is also inappropriately switched on in many cancers, including medulloblastoma.

"At this point we asked whether we could affect the development of medulloblastoma in mice by shutting down Atoh1," Zoghbi said.

To find out, the team applied their local Atoh1-shutdown technique to a special strain of mice with a specific genetic mutation that makes them develop medulloblastoma. In these mice, a mutant gene is switched on after birth, sending the Sonic Hedgehog signaling pathway into overdrive, causing precancerous lesions and tumors in the cerebellum. But when Zoghbi's team switched off Atoh1, these cancerous changes never occurred.

Establishing Atoh1 as a key player in the origin of medulloblastoma makes it a potential target for new drug treatments, Zoghbi said. But to Zoghbi, an important next step is to determine whether the protein is still needed to keep tumors growing after they've become established: "If we allow these tumors to develop, and then we take away Atoh1, would that make a difference?" Her lab and others are also now racing to determine what keeps Atoh1 inappropriately switched on in medulloblastoma cells, and what normally switches it off.

Zoghbi emphasized that she originally took up the study of Atoh1 as an exercise in pure biology, with no idea that it would have relevance to disease. "That just underscores the tremendous importance of doing science for science's sake," she said.

Jim Keeley | EurekAlert!
Further information:
http://www.hhmi.org

More articles from Life Sciences:

nachricht Modern genetic sequencing tools give clearer picture of how corals are related
17.08.2017 | University of Washington

nachricht The irresistible fragrance of dying vinegar flies
16.08.2017 | Max-Planck-Institut für chemische Ökologie

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Fizzy soda water could be key to clean manufacture of flat wonder material: Graphene

Whether you call it effervescent, fizzy, or sparkling, carbonated water is making a comeback as a beverage. Aside from quenching thirst, researchers at the University of Illinois at Urbana-Champaign have discovered a new use for these "bubbly" concoctions that will have major impact on the manufacturer of the world's thinnest, flattest, and one most useful materials -- graphene.

As graphene's popularity grows as an advanced "wonder" material, the speed and quality at which it can be manufactured will be paramount. With that in mind,...

Im Focus: Exotic quantum states made from light: Physicists create optical “wells” for a super-photon

Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.

Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...

Im Focus: Circular RNA linked to brain function

For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.

While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...

Im Focus: RAVAN CubeSat measures Earth's outgoing energy

An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.

The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...

Im Focus: Scientists shine new light on the “other high temperature superconductor”

A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.

Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Call for Papers – ICNFT 2018, 5th International Conference on New Forming Technology

16.08.2017 | Event News

Sustainability is the business model of tomorrow

04.08.2017 | Event News

Clash of Realities 2017: Registration now open. International Conference at TH Köln

26.07.2017 | Event News

 
Latest News

Gold shines through properties of nano biosensors

17.08.2017 | Physics and Astronomy

Greenland ice flow likely to speed up: New data assert glaciers move over sediment, which gets more slippery as it gets wetter

17.08.2017 | Earth Sciences

Mars 2020 mission to use smart methods to seek signs of past life

17.08.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>