Expression of guanylin is downregulated in mouse and human intestinal adenomas

Guanylin is a pro-secretory hormone that is expressed in intestinal epithel ia. Previously, we mapped the guanylin gene to mouse and human chromosomal regions containing multiple intestinal tumor-modifying loci. Here, we inves tigate whether guanylin expression is downregulated in precancerous human a nd mouse intestinal adenomas and whether diminished guanylin expression inc reases adenoma susceptibility in an animal model of intestinal cancer, the multiple intestinal neoplasia (Min) mouse. In situ hybridization analysis i ndicated diminished guanylin expression in both mouse and human adenomas, N orthern analysis of mouse intestinal tissues showed strain-specific levels of guanylin expression but no correlation with the resistance or susceptibi lity of each strain to adenoma formation. Similarly, cDNA sequence analysis indicated no inactivating mutations or polymorphisms common to either the high or low adenoma-risk groups. Nonetheless, we have shown that significan t loss of guanylin RNA in adenomas of mouse and human is a marker of intest inal epithelial cell transformation. (C) 2000 Academic Press.