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Gene-silencing study seeks cancer genes
By Adam Marcus

One of the hottest genetics tools in laboratories these days is RNA. By adding this molecule to cells, scientists can turn off individual genes and see what happens when they're silent. Known as RNA interference (RNAi), it has been used to study thousands of genes in worms and other model organisms.

A large-scale effort is now underway to use the tool in some 8,000 human genes, with the hope of finding those implicated in cancer.

The effort, a partnership between Cancer Research U.K. and the Netherlands Cancer Institute, will screen a variety of tumor cell lines, including breast, lung and pancreatic cancers.

Julian Downward, a molecular biologist at Cancer Research UK, and leader of the project, says a pilot study of 300 genes showed that RNAi reduces the activity of the genes it targets by an average of 70 to 80 percent. Because cancer tumor drugs don't completely shut down the activity of their targets, either, Downward says that rate is a good mimic of the effectiveness of tumor therapies.

In addition to studying what individual genes do, the researchers will also be looking for cells that can overcome the loss of silenced genes. Such cells could help explain why some tissue becomes malignant, and knowing their genetic secrets could lead to highly selective and potent anti-tumor drugs. "Nine out of ten things you would do to a tumor cell to stop it growing would also kill a normal cell," Downward says.

Once the 8,000 genes have been studied, the researchers plan to analyze all 30,000-odd genes in the human genome. By the end of the project, Downward says, they should have a roster of between 200 and 300 genes involved in cancer.

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