Genetic Clue in Down Syndrome may help cancer research

Down syndrome (DS) is a chromosomal disorder caused by an error in cell division that results in an additional third copy of chromosome 21. Although people with DS have a greater chance of developing leukaemia; the incidences of most solid-tumour cancers, including brain, lung, breast and bone cancers are 10 percent lower than in the general population. Given that they have an extra copy of the chromosome 21, researchers have theorized that people with DS may benefit from an extra dose of one or more cancer-protecting genes.
The late Dr Folkman’s popularized notion that people with DS might be benefiting from a gene that blocks angiogenesis, which is the process responsible for the development of blood vessels that are essential for cancer’s growth. Cancer researcher Sandra Ryeom, and colleagues from the children’s vascular biology program believe that there may be four or five genes on chromosome 21 that are necessary for angiogenesis suppression
Ryeom and her colleagues used induced pluripotent stem cells from a volunteer with DS to successfully genetically engineer mice with a third copy of the chromosome 21, and subsequently extra versions of 231 different genes. In this mouse model of DS, an extra copy of the gene Dscr1 was found to sufficiently suppressed signalling by the angiogenesis-promoting protein vascular endothelial growth factor (VEGF), which resulted in decreased growth of endothelial cells(which compose blood vessel walls). An extra copy of another chromosome 21 gene, Dyrk1A, also appeared to suppress VEGF signalling, via blocking the “calcineurin-signaling pathway”. The blocking of VEGF signalling suppresses the ability of endothelial cells to grow and form vessels. By stopping blood vessel formation it not only starves the tumor, but stops metastasis, where the tumour cells enter the bloodstream and relocate somewhere else.
Ryeom and her colleagues also worked with induced pluripotent stem cells from skin cells of patients with DS to validate and confirmed that the suppression of angiogenesis, in mouse models, by an extra copy of the genes Dscr1 and Dyrk1A also holds true in humans.
Ryeom's group has identified which part of the DSCR1 protein blocks calcineurin and is hoping to develop immunosuppressive drugs that target the calcineurin in endothelial cells, without affecting the calcineurin pathways in other cells and causing side effects

Original link: http://www.news-medical.net/news/2009/05/20/People-with-Down-syndrome-may-have-more-cancer-protective-genes.aspx