A Protein to Give Ulcers Ulcers

Shamrock-shaped proteins play a key role in preventing ulcers and other intestinal disorders, according to two studies published today in Science. The finding, scientists say, could lead to drugs for treating a range of gastrointestinal-tract problems.

One protein, called intestinal trefoil factor (ITF), is normally produced in the small and large intestines. Scientists at Massachusetts General Hospital found that genetically engineered mice that do not produce the protein died from colitis when they were exposed to a chemical that irritates the intestinal wall but only causes only mild mucosal damage in normal mice. Previous studies have shown that ITF in normal rats helps ward off damage to the GI tract from common irritants such as alcohol and indomethacin, a drug similar to Motrin.

A second member of the "three-leaf" family, pS2 trefoil protein, seems to play an unexpected role: protecting against tumors. Researchers at the Centre National de la Recherche Scientifique in Paris created a strain of mice lacking pS2. The animals developed stomach tumors, of which 30% were malignant. The result seems to indicate that pS2 plays a role in suppressing tumor growth, which is surprising, as scientists had thought that trefoil proteins stimulate cell growth. The study has "opened up a whole new debate" on the role of these proteins, says Vanderbilt molecular biologist Rebecca Chinery.

These two studies have also opened up pharmaceutical possibilities: Trefoil proteins are remarkably stable and could be taken orally, Chinery says. Moreover, massive quantities of trefoils do not appear to harm mice.