Protected. People with Down syndrome are less likely to develop cancer.
George Doyle / Stockbyte
Down syndrome causes mental retardation and a host of health problems. But it also seems to protect people against cancer. Researchers have now found a potential genetic mechanism of this protective effect. The findings could one day lead to cancer prevention treatments in the general population.
People with Down syndrome have three copies of chromosome 21 instead of the standard two. This means they have an extra copy of each of the 231 genes on this chromosome. Because studies have suggested that these people also have a lower incidence of colon, breast and other solid tumor cancers, researchers have long wondered if any of these additional genes might confer protection. Last year, geneticist Roger Reeves of Johns Hopkins University in Baltimore, Maryland, and colleagues found that the version of the mouse one of tripled genes - called Ets2 - suppresses the formation tumors in mice, although the mechanism remains unclear ( science NOW, January 2, 08).
The new findings suggest another gene and a clear mechanism. Researcher Sandra Ryeom Cancer Hospital Boston Children and colleagues target a gene on chromosome 21 called DSCR1 (also known as RCAN1 ). Previous work suggested that the protein produced by this gene interferes with the formation of blood vessels, or angiogenesis. Inhibition of angiogenesis is a strategy to stop the growth of the tumor, so Ryeom and his colleagues wondered if this could happen in Down syndrome.
To investigate, the researchers first examined the human fetal tissue electively aborted to see if the gene was overactive in people with Down syndrome. It was: DSCR1 protein levels were 1.8 times higher than normal. Next, the team created a strain of mice with an extra copy of the version of the mouse DSCR1 gene. An additional copy of this gene alone was enough to suppress angiogenesis and inhibit the growth of transplanted tumors in these mice, reports the team in issue tomorrow Nature .
"This is a really interesting what we know about the resistance to tumors" in people with Down syndrome, said Reeves. He and Ryeom agree that the protective effects of DSCR1 and Ets2 probably different mechanisms, with Ets2 acting at an early stage before tumors are large enough initiate angiogenesis. And there are probably other genes implicated in the protective effect, said Ryeom.
Ryeom hope the findings will lead to better cancer treatment strategies in the general population. Drugs that inhibit angiogenesis have generated much hope (and hype) in the late 190s, but success so far has been modest. This new point working components of the signaling pathway of angiogenesis could be more effective target of the drug, said Ryeom. Otherwise, she said, blocking angiogenesis could function better as a preventive measure than as a cure. Compounds that block angiogenesis are relatively non-toxic to adults, Ryeom notes, and she thinks it might be possible to develop a low-dose anticancer drug that people might take as a vitamin. The idea is good biological sense, but there would be serious regulatory hurdles for any drug to be used before people develop cancer, said David Threadgill, a geneticist at the State University North Carolina in Raleigh.
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