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Restoring silenced suppressor gene kills lung-cancer cells

g in cells making up many lung tumors, and in 62 percent of cases, the gene is turned off by a chemical process known as methylation.

"There is nothing wrong with those genes except that they are silenced by methylation," Huebner says. "Experimental drugs are now being tested that cause demethylation and may reactivate WWOX and other genes."

For this study, Huebner and her colleagues used three different lines of laboratory-grown lung-cancer cells that were missing WWOX protein. The researchers then used a virus engineered to carry working copies of the WWOX gene into the three cell lines.

After five days, the researchers found that cells having an active WWOX gene died off. The cells self-destructed through a natural process known as programmed cell death, or apoptosis. The lung-cancer cells that lacked the WWOX gene, on the other hand, continued growing and increased in number nearly five- or six-fold.

Next, the researchers took some of the lung-cancer cells to which they'd added working copies of the WWOX gene, and they transplanted the cells into mice; a second group of control mice received lung-cancer cells without the WWOX gene.

After 28 days, the mice that received tumor cells with no WWOX gene had developed tumors. Of the mice that received tumor cells with the gene, 60 percent in one group and 80 percent in another group showed no tumors.

"Our study is a proof of principle," Huebner says. "It shows that if the WWOX gene can be delivered into tumor cells, it can kill them.

"We also showed that if a silenced WWOX gene is present and can be turned back on, that too will kill tumor cells," adds first author and postdoctoral researcher Muller Fabbri.

"We don't believe that using WWOX as a therapy will necessarily eradicate tumors, Fabbri says, "but we do believe that this kind of gene therapy might be useful when used in combination with chemotherapy and other therapies."


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Source:Ohio State University


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