Main Category: Neurology / Neuroscience
Also Included In: Cancer / Oncology; Stem Cell Research
Article Date: 14 Aug 2013 – 0:00 PDT
If you write about specific medications or operations, please do not name health care professionals by name.
Johan Holmberg, PhD, at the Ludwig Institute for Cancer Research Stockholm took a close look at the role of the CHD5 tumor suppressor during normal nervous system development. Previous studies had shown that the gene CHD5 is often inactivated in the most severe forms of neuroblastoma, but little was known about its function in healthy tissue or how it operates. The study, which was conducted in close collaboration with colleagues at Trinity College, Dublin, Ireland, addressed these two key issues.
The researchers also dissected how CHD5 operates, showing that it sticks to certain modifications of histone proteins. These modifications help control how genes are turned on and off. In the absence of CHD5, key stem cell genes are not turned off, and genes required for neuronal maturation are not turned on. The findings highlight how the failure of a cell to properly mature into its terminal state can underlie cancer, a relatively understudied area of research.
For any corrections of factual information, or to contact the editors please use our feedback form.
Please send any medical news or health news press releases to:
“The result was a complete absence of neurons,” says Ludwig researcher Holmberg who is based at the Karolinska Institutet. “Instead of becoming neurons, the cells with CHD5 knocked down stayed in a limbo-like state between an actively-dividing stem cell and a mature nerve cell. It was a very robust effect,” added Holmberg.
MLA
Developmental Cell, Volume 26, Issue 3, 223-236, 12 August 2013. 10.1016/j.devcel.2013.07.008
CHD5 Is Required for Neurogenesis and Has a Dual Role in Facilitating Gene Expression and Polycomb Gene Repression
The research could also lead to new ways to treat neuroblastoma, perhaps using currently approved drugs. One component of neuroblastoma treatment is retinoic acid, a drug that can drive neuronal maturation. Holmberg and his colleagues found that knocking down the expression of CHD5 in more benign neuroblastoma cells blocked their capacity to mature in response to retinoic acid treatment. “These cells were completely insensitive to treatment, no matter how much we gave them, mirroring the same unresponsiveness to retinoic acid in the more malignant CHD5-negative neuroblastoma cells,” says Holmberg.
Ludwig Institute for Cancer Research
neurology / neuroscience section for the latest news on this subject.
