Down Syndrome protein reduces tu...( Bethesda MD Scientists have found tha...)

Bethesda, MD Scientists have found that overexpression of a protein called Down Syndrome Critical Region 1 (DSCR-1) blocks the formation of new blood vessels and thus reduces tumor growth. Therapeutics based on this finding may potentially lead to new cancer treatments.

The research appears as the "Paper of the Week" in the November 26 issue of the Journal of Biological Chemistry, an American Society for Biochemistry and Molecular Biology journal.

Many vascular disorders including atherosclerosis, tumor growth, and inflammation are caused by the activation and dysfunction of the endothelium. This layer of cells lines the inside of blood vessels and regulates many processes including new blood vessel formation, blood vessel diameter, blood clotting, the migration of circulating white blood cells, and the normal release of molecules involved in inflammation

"Because endothelial cells are so active, any perturbation in their function may have undesirable effects," explains Dr. Takashi Minami of the University of Tokyo. "Indeed, endothelial cell dysfunction underlies many disease states in humans, including--but certainly not limited to--stroke, coronary artery disease, cancer and preeclampsia. An important goal in vascular research is to develop new strategies that inhibit endothelial cell dysfunction and abnormal blood vessel formation."

Certain agonists, such as vascular endothelial growth factor and the serine protease thrombin, cause endothelial cells to increase their expression of genes involved in proliferation, inflammation, and thrombosis. Dr. Minami and his colleagues found that these agonists also turn on a gene that produces Down Syndrome Critical Region 1 (DSCR-1), and that DSCR-1 then negatively feeds back on the agonists and shuts off their production. Thus, DSCR-1 acts as a circuit breaker in agonist signaling, and serves in a negative feedback loop to inhibit endothelial cell activation and growth.

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Contact: Nicole Kresge
nkresge@asbmb.org
301-634-7415
American Society for Biochemistry and Molecular Biology
19-Nov-2004

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