The protein called Fbw7 is a key element in controlling cyclin E, another protein involved in control of cell proliferation. “High levels of cyclin E in breast tumors are indicators of poor prognosis,” said Dr. Stephen Elledge, professor of molecular biology and biochemistry and a Howard Hughes Medical Institute researcher at Baylor. Elledge and Dr. J. Wade Harper are senior authors of a paper on the research published on the Science Express web site, Aug. 31. Their laboratories participated equally in the work.
“Cells that make too much cylin E are constantly proliferating and are genetically unstable,” Elledge said. The protein found in Elledge’s laboratory -- Fbw7 – controls the levels of cyclin E in cells. “If you interfere with its function in Drosophila (fruit fly) tissue culture cells or in human cells, the cyclin E levels become very high,” he said. “It truly is a regulator of cyclin E.”
In addition, the researchers found that the laboratory breast cancer-derived cell cultures that made the most cyclin E failed to make Fbw7 at all. “This (the gene that is the code for production of Fbw7) is very probably a tumor suppressor gene,” Elledge said.
Genes are associated with the production of specific proteins. Tumor suppressor genes and their associated proteins work to prevent cellular changes that can cause tumors. When something interferes with the action of the gene – such as a mutation – the process of cancer can begin at the cellular level.
Researchers who worked on the project include Drs. Harper, Deanna M. Koepp, Laura K. Schaefer, Xin Ye, and Claire Chu. The work is the result of collaboration between the laboratories of Elledge and Harper. Dr. Khandan Keyomarsi of The University of Texas M.D. Anderson Cancer Center was also an author of the paper and contributed to the work dealing with breast cancer cells.
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