Silenced Gene May Treat Cancer

Restoring a gene often silenced in lung cancer causes the cells to self-destruct, suggesting a new strategy for treating the disease.

Researchers focused on a gene known as WWOX, which is silenced in a large majority of lung cancers as well as in cancers of the breast, ovary, prostate, bladder, esophagus, and pancreas. In both laboratory and animal experiments, restoring the silenced WWOX gene slowed or stopped the cells' growth. These findings were published in the October 13, 2005, online edition of the Proceedings of the [U.S.] National Academy of Sciences.

WWOX is a tumor-suppressor gene. The WWOX protein is missing in cells making up many lung tumors, and in 62% of cases, the gene is turned off by a chemical process known as methylation. In the current study, researchers used three different lines of laboratory-grown lung-cancer cells that were missing WWOX protein. They engineered a virus to carry working copies of the WWOX gene into the three cell lines. After five days, cells having an active WWOX gene died, self-destructed by apoptosis. In contrast, the lung cancer cells that lacked the WWOX gene continued growing and increased in number nearly five-fold or six-fold.

The researchers also took some lung-cancer cells to which they had added working copies of the WWOX gene and transplanted the cells into mice. A 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% in one group and 80% in another group showed no tumors.

"Our study is a proof of principle,” said co-author Kay Huebner, professor of molecular biology, immunology, and medical genetics at the Comprehensive Cancer Center at Ohio State University (OSU, Columbus, USA).

"We don't believe that using WWOX as a therapy will necessarily eradicate tumors,” added first author Muller Fabbri, a postdoctoral fellow at OSU, "but we do believe that this kind of gene therapy might be useful when used in combination with chemotherapy and other therapies.”