Scientists at Jefferson Medical College (JMC) appear to have an important clue to the workings of a gene that normally protects against cancer, the FHIT gene. Ultimately, by understanding how FHIT works, scientists may be able to find ways to interfere with the development of cancer.
Charles M. Brenner, PhD, Assistant Professor of Microbiology and Immunology, JMC, and a member of Jefferson's Kimmel Cancer Center, and his colleagues at Jefferson and the University of Texas in San Antonio and at the University of Sheffield in England, are pursuing the study.
A report of the researchers' work was published in May in The Proceedings of the National Academy of Sciences.
In February 1996, a team of scientists led by Kay Huebner, PhD, Professor of Microbiology and Immunology at JMC and the Kimmel Cancer Center, and Carlo M. Croce, MD, Professor and Chairman of the Department of Microbiology and Immunology, JMC, and Director of the Kimmel Cancer Center, announced that they had identified the FHIT gene. The researchers have found that the FHIT gene is frequently inactivated early in the development of several types of cancer, especially lung cancer.
To study the possible links between inactive FHIT genes and early cancer growth, Dr. Brenner's team focuses on the product of the FHIT gene, the tumor-suppressing Fhit protein.
Tumors form when the Fhit protein is absent. So Dr. Brenner and his co-workers are seeking to understand how tumors are suppressed when the Fhit protein is present. Tumor suppression appears to correlate with the ability of Fhit to bind a cellular factor. Dr. Brenner's group has succeeded in determining the 3D structure of Fhit bound to that cellular factor.
"The genetic changes that Drs. Huebner and Croce discovered in the FHIT gene appear to be the primary mechanism by which FHIT becomes inactivated in cancer," according to Dr. Brenner. "The structural changes we have described appear to be the way in which the Fhit protein becomes activated in normal cells responding to their enviroment."
The research team's aim is to follow the entire "cellular pathway from activation of Fhit protein to the ultimate events that arrest the growth of cells and keep them from forming tumors," Dr. Brenner says. The team's eventual goal is to develop chemical treatments that would emulate the tumor-suppressing function of Fhit or kill cells that are missing Fhit.
Dr. Brenner's work is funded by the National Cancer Institute, the March of Dimes Birth Defects Foundation, the Burroughs Wellcome Foundation and the Arnold and Mabel Beckman Foundation.