Tracking busy genes to get at cancer.

By identifying which genes are overactive in certain breast tumors, researchers have discovered a genetic signature that could help doctors predict if and when a woman's cancer might spread to her lungs. The findings could also clarify how proteins encoded by these genes orchestrate the cancer's movement in the body, or metastasis, says Andy J. Minn, an oncologist at the University of Chicago. He and his colleagues at Memorial Sloan-Kettering Cancer Center in New York report the work in the July 28 Nature.

While bone is the most common destination for roving breast cancer cells, metastases to the lung are more deadly, Minn says. To decipher the genetic signature for this especially lethal form of the cancer, he and his colleagues identified 54 genes that were highly active in breast cancer cells prone to spread to the lungs.

Among these genes, the researchers chose nine that they suspected of having roles in rendering cells cancerous. Then, they conducted tests on mice to determine what roles, if any, the proteins encoded by the genes might play in lung metastasis.

Minn and his coworkers first obtained cells from various breast tumors. In some women, these cancers later spread to the lungs. When the researchers injected the cells from those women into the bloodstreams of mice or into the animals' mammary tissue, the cancer cells found their way to the animals' lungs.

But when the scientists shut down the nine cancer-related genes--individually or in various combinations--the cells didn't spread as readily to the animals' lungs or didn't grow well there. The preliminary data suggest that certain proteins encoded by these genes facilitate metastasis, while others confer a survival advantage to a tumor cell in the lung. If borne out, the findings could lead to a way to predict which cases of cancer will spread or relapse.

Identifying these proteins might offer pharmaceutical companies targets for drugs, Minn says.