NEW YORK (Reuters Health) - Downregulation of the forkhead nuclear factor FOXO3a by the enzyme Ik beta kinase (IKK beta) may be a key mechanism for promoting tumor cell growth and tumorigenesis in breast cancer, Texas-based researchers report. Absence of downregulation is thus an encouraging sign.
As investigator Dr. Mien-Chie Hung told Reuters Health, “The expression of the longevity gene, FOXO3a could be a good prognosis indicator to predict the survival of breast cancer patients.” Moreover, because of its oncogenic activity, IKK beta “could serve as a target for development of cancer treatment.”
The protein kinase Akt is known to regulate FOXO factors. However, IKK beta can inhibit FOXO3a independently of Akt, the researchers report in the April 16th issue of Cell.
Dr. Hung and colleagues at the University of Texas, Houston, came to this conclusion after a series of studies in mice “strongly” suggested that “FOXO3a has a general suppression effect for tumorigenesis in vivo.”
The found that FOXO3a was present in 113 of 131 tumor cells samples from breast cancer patients. FOXO3a was inactive in 83 samples and active in the remaining 30.
Overall, the team saw that “nuclear exclusion of FOXO3a correlates with expression of IKK beta and phosphorylated AKt in tumors and normal tissues and is associated with poor survival in breast cancer.”
Moreover, Dr. Hung concluded, a mutant of FOXO3a, which the investigators developed during these studies, “could serve as a potential candidate for gene therapy to treat human cancers”.
Source: Cell 2004;117:225-237. [ Google search on this article ]
MeSH Headings:Biological Sciences: Biology: Breast Neoplasms: Gene Expression Regulation: Genetics: Genetics, Biochemical: Molecular Biology: Neoplasms: Neoplasms by Site: Nuclear Proteins: Gene Expression Regulation, Neoplastic: Biological Sciences: DiseasesCopyright © 2002 Reuters Limited. All rights reserved. Republication or redistribution of Reuters content, including by framing or similar means, is expressly prohibited without the prior written consent of Reuters. Reuters shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon. Reuters and the Reuters sphere logo are registered trademarks and trademarks of the Reuters group of companies around the world.
