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Findings give insight into how colon cells transform into precancerous polyps

A key signaling pathway appears to be critical to the earliest transformation of normal colon cells into growths called polyps that may advance to colon tumors, Vanderbilt-Ingram Cancer Center scientists have reported.

The findings suggest that, someday, doctors might use drugs that interrupt this pathway to treat individuals who are found to have colon cells on the verge of this transformation. The goal would be to prevent polyps -- and thus colon cancer -- from ever developing.

"Clearly, were a long way from doing that, but the prospects are very exciting," said Dr. Robert J. Coffey, Ingram Professor of Cancer Research and professor of Medicine and Cell Biology. Coffeys laboratory, in collaboration with the laboratory of David Threadgill, Ph.D., reported their findings recently in the Proceedings of the National Academy of Sciences.

The signalling pathway involves the epidermal growth factor receptor and the "ligands" that bind to it. The receptor sits across the cell surface, much like a satellite dish. The ligand fits into the receptor to transmit signals into the cell that prompt its growth. Scientists are focused on this pathway as more is learned about how it is involved in cancer development and progression and as new drugs are developed to interrupt it.

The Vanderbilt work helps clarify contradictory findings reported more than a year ago by two different groups. One group observed a 90 percent reduction in polyp formation when they used an inhibitor of EGFr in Min mice, a strain that is genetically engineered to develop hundreds of colon polyps. The other group did a similar experiment with a similar drug and found no effect.

So the Vanderbilt researchers instead turned to genetics. They took advantage of a mouse called waved2 that has a naturally occurring mutation in the EGFr tyrosine kinase domain (the section beneath the cell surface) that results in a 90 percent reduction in EGFr activity. These
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Contact: Cynthia Manley
cynthia.manley@mcmail.vanderbilt.edu
615-354-0936
Vanderbilt University Medical Center
19-Apr-2002


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