Once they had established that inactivated FOXO3 protein could lead to cancer, the researchers examined its role in tumor cells from 131 breast cancer patients. They found FOXO3 in 113 out of 131 samples. Of the 113 samples with FOXO3, the protein was inactive in 83 and active in 30 samples. When they looked at patient survival, they found a strong correlation between active FOXO3 and better patient survival. Additional research revealed the FOXO3 protein can be found in patients with stomach, liver and lung cancer. However, the scientists did not study enough of these patient samples to say how important the gene is in these cancers.

In additional laboratory studies, the scientists demonstrated that a slightly altered form of FOXO3 that can ™t be inactivated by IKK acts as an even more potent tumor suppressor than the normal FOXO protein.

This mutant FOXO3 may be an even more powerful tumor suppressor than the normal FOXO3 protein, says Hung. This finding may provide a new avenue for cancer gene therapy or other targeted cancer therapies.

The presence of active Forkhead (FOXO) protein has been linked to longevity in laboratory animals such as the nematode worm, says Hung. Hu and Hung ™s discovery that FOXO3 is a tumor suppressor may provide a clue to the gene ™s ability to increase lifespan in animals. But exactly how a tumor suppressor could increase lifespan remains a mystery.

That is the million-dollar question, Hung says.

The research was supported by grants from the National Institutes of Health, the M. D. Anderson Breast Cancer Research Program, the Susan G. Komen Breast Cancer Foundation, and a Cancer Center Supporting Grant. All authors of the study, who included Dung-Fang Lee, Weiya Xia, M.D., Jer-Yen Yang, Yiyu Zou, Ph.D., Shilai Bao, Ph.D., and Ryuji Kobayashi, Ph.D., are of the M. D. Anderson Cancer Center.