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Jefferson Scientists Hopeful That Understanding Tumor-Suppressor Protein Function May Someday Lead To Treatment

Scientists at Jefferson Medical College of Thomas Jefferson University in Philadelphia appear to have an important clue to the workings of a gene that normally protects against cancer. Ultimately, by understanding how both the normal and the damaged gene work, scientists may be able to find ways to interfere with the development of cancer.

Charles Brenner, Ph.D., assistant professor of microbiology and immunology, and a member of Jefferson's Kimmel Cancer Center, and his colleagues at the University of Texas in San Antonio, and at the University of Sheffield in England, have distinguished between potential mechanisms by which the FHIT gene works in preventing cancer development.

A report of the researchers' work appears May 12 in the Proceedings of the National Academy of Sciences.

Dr. Brenner and his colleagues used a combined genetic, biochemical and crystallographic approach to gain information about the function of the tumor-suppressor protein, Fhit, the product of the FHIT gene.

According to Dr. Brenner, Fhit is "encoded in the most fragile site of the human genome. The FHIT gene is frequently inactivated early in the development of cancer, especially in lung cancer."

Dr. Brenner and his co-workers sought to understand how the Fhit protein suppresses tumor formation. "We knew that the Fhit protein is an enzyme that binds and cleaves an unusual class of nucleotides in the cell, called ApppA," he explains. "We wanted to determine if the important function of Fhit was to cleave ApppA or signal the presence of this compound in the cell in order to put the brakes on cell growth." Tumors form when the Fhit protein is absent.

New experiments showed that altered forms of the Fhit protein that bind but don't cleave ApppA are actually still working in tumor suppression. "That excluded the idea that the important thing that Fhit
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Contact: Steve Benowitz
steven.benowitz@mail.tju.edu
215-955-6300
Thomas Jefferson University
11-May-1998


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