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
|Contact: Jim Keeley|
Howard Hughes Medical Institute