"This suggests that an important step in the development of cancer is turning down the gene responsible for production of CUGBP2, thereby reducing CUGBP2 protein levels and allowing the cancer to flourish," Anant explains.

The researchers also found that when CUGBP2 attached to mRNA from COX-2, cancer cells no longer could make COX-2, and they died. That suggested that CUGBP2 might play a central role in tumor cell survival or death.

"CUGBP2 may be one type of master switch used by the cell to control other key proteins," says co-author Brian K. Dieckgraefe, M.D., Ph.D., assistant professor of medicine in the Division of Gastroenterology. "Proteins like COX-2 need to be tightly regulated to avoid uncontrolled growth. That may be why CUGBP2 levels were significantly lower in every single tumor we studied."

Anant, Dieckgraefe and colleagues also found that CUGBP2 was not toxic to healthy cells. Moreover, when they introduced CUGBP2 into cancer cells at the levels found in normal cells, the cancer cells died.

"When CUGBP2 is introduced, there are a number of molecular derangements that take place in the cancer cell that make it susceptible to death," Anant says. "In the future, it may be possible to use this protein as a means of killing tumor cells without harming normal cells because normal cells already produce significant amounts of the protein."

Anant already is looking at whether it is possible to use the protein in animal models of cancer to see whether it has the same effect in their tumors as it did in human cancer cells in the test tube. If these studies continue to demonstrate that it's possible to kill cancer cells by raising CUGBP2 levels, Anant believes the strategy might be ready for human testing in a few years.

Even if raising levels of CUGBP2 does not eliminate cancer, t
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Contact: Jim Dryden
drydenj@msnotes.wustl.edu
314-286-0110
Washington University School of Medicine
17-Jan-2003