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 Decoding the genome's cryptic language
27.02.2017 | University of California - San Diego

nachricht New risk factors for anxiety disorders
24.02.2017 | Julius-Maximilians-Universität Würzburg

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Safe glide at total engine failure with ELA-inside

On January 15, 2009, Chesley B. Sullenberger was celebrated world-wide: after the two engines had failed due to bird strike, he and his flight crew succeeded after a glide flight with an Airbus A320 in ditching on the Hudson River. All 155 people on board were saved.

On January 15, 2009, Chesley B. Sullenberger was celebrated world-wide: after the two engines had failed due to bird strike, he and his flight crew succeeded...

Im Focus: Breakthrough with a chain of gold atoms

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

Im Focus: DNA repair: a new letter in the cell alphabet

Results reveal how discoveries may be hidden in scientific “blind spots”

Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...

Im Focus: Dresdner scientists print tomorrow’s world

The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.

The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...

Im Focus: Mimicking nature's cellular architectures via 3-D printing

Research offers new level of control over the structure of 3-D printed materials

Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Booth and panel discussion – The Lindau Nobel Laureate Meetings at the AAAS 2017 Annual Meeting

13.02.2017 | Event News

Complex Loading versus Hidden Reserves

10.02.2017 | Event News

International Conference on Crystal Growth in Freiburg

09.02.2017 | Event News

 
Latest News

New pop-up strategy inspired by cuts, not folds

27.02.2017 | Materials Sciences

Sandia uses confined nanoparticles to improve hydrogen storage materials performance

27.02.2017 | Interdisciplinary Research

Decoding the genome's cryptic language

27.02.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>