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Study of fruit flies may yield new clues to colon cancer development

CHAPEL HILL - A study of fruit flies by scientists at the University of North Carolina at Chapel Hill may yield new clues to human colon cancer development.

A report of the study, the cover story for the September 20 issue of the Journal of Cell Biology, focuses on the tumor suppressor protein adenomatous polyposis coli, or APC. Originally identified in people with familial colon cancer, APC mutations are found in a majority of colon tumors.

According to senior study author Dr. Mark Peifer, UNC-CH associate professor of biology and a member of UNC Lineberger Comprehensive Cancer Center, APC plays an important role within cells to help destroy another protein, beta catenin. His research confirms that in fruit flies (Drosophila), it functions against a very similar protein, Armadillo.

"Beta catenin transmits signals from the cell surface to the nucleus," Peifer explains. "Normally, beta catenin levels in colon cells are very low because it gets rapidly destroyed."

Studies have found that mutations to APC disrupt the beta catenin destruction signaling machinery. Genes along the pathway are fixed permanently to "ON" and beta catenin cellular levels rise. In the cell nucleus this triggers a molecular chain of events that in mammals leads to cell proliferation and tumor formation.

"During normal development, cells are talking to one another, sending signals to a neighbor for a short period of time, at the right time and at the right place. Occasionally, a mutation can switch the signaling pathway to an 'ON' state for good. And that often causes trouble," Peifer says.

"The cancer connection in the signaling pathway we study was first made in colon cancer, one of the most important human malignancies because it is one of the most prevalent," Peifer notes. "It's probably the most prevalent that's not easy preventable. If people didn't smoke, colon cancer might be the most common malignancy."

In the new study, Peifer a
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Contact: Lynn Wooten
Lwooten@unch.unc.edu
919-966-6046
University of North Carolina School of Medicine
20-Sep-1999


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