Pml could help control brain cancer
13 February 2009
People suffering from cancers of the nervous system may have a better chance of containing the disease with the involvement of the tumour suppressor protein promyelocytic leukemia (Pml), new research published in the journal Nature Neuroscience suggests.
Scientists at the Medical Research Council Toxicology Unit at the University of Leicester found Pml has a role in controlling the function of neural progenitor cells (stem cells) in the developing brain. This new understanding means Pml could play a tumour suppressing role in cancers of the nervous system.
One of the authors of the study, Paolo Salomoni, said: “We wanted to explore Pml role in neural stem cells and we found a new role for Pml in the nervous system. Our research uncovered that Pml expression is restricted to neural stem cells of the developing neocortex.” Pml was previously only known to be associated with the blood and other non-neural tissues.
The scientists showed that during neurogenesis, the time when neurons are made, Pml is expressed in NPCs but is excluded from mature neurons.
“When we compared mouse embryos we found smaller brains and a substantial decrease in neocortical wall thickness present in Pml mutants. This was accompanied by an increase in the number of neural stem cells. The reduction in mutant brain size continued during adulthood which indicated Pml was an integral part of brain development.
“We found Pml’s regulation of cell growth at the level of neural stem cells in the developing brain meant it functionally interacted with the Retinoblastoma protein (pRb), a tumour suppressor dormant in many types of cancer. pRb has been shown to play a necessary role during neocortical development.
“In summary, our findings clearly implicate the tumour suppressor Pml in the regulation of cell fate in the nervous system and more generally constitute a novel contribution to our understanding of the mechanistic regulation of brain development.”
Original research paper: The tumor suppressor Pml regulates cell fate in the developing neocortex is published in Nature Neuroscience 2009 12:132-140.
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