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Why Do People With Down Syndrome Have Less Cancer?
The late cancer researcher Judah Folkman, MD, founder of the Vascular Biology Program at Children's Hospital Boston, popularized the notion that they might be benefiting from a gene that blocks angiogenesis, the development of blood vessels essential for cancer's growth, since their incidence of other angiogenesis-related diseases like macular degeneration is also lower. A study from Children's confirms this idea in mice and human cells and identifies specific new therapeutic targets for treating cancer.
Publishing online May 20 in the journal Nature, cancer researcher Sandra Ryeom, PhD, and colleagues from Children's Vascular Biology Program show that a single extra copy of Dscr1 (one of the 231 genes on chromosome 21 affected by trisomy, with three copies rather than two) is sufficient to significantly suppress angiogenesis and tumor growth in mice, as well as angiogenesis in human cells. The team also found its protein, DSCR1, to be elevated in tissues from people with Down syndrome and in a mouse model of the disease.
Further study confirmed that DSCR1 acts by suppressing signaling by the angiogenesis-promoting protein vascular endothelial growth factor (VEGF). In a mouse model of Down syndrome, endothelial cells (which make up blood vessel walls) showed a decreased growth response to VEGF when they had an extra copy of Dscr1. An extra copy of another chromosome 21 gene, Dyrk1A, also appeared to decrease cells' response to VEGF.
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