Expression of Guanylin Is Downregulated in Mouse and Human Intestinal Adenomas

• Published in: Biochemical and biophysical research communications 2000-06, Vol.273 (1), p.225-230
• Main Authors: Steinbrecher, Kris A, Tuohy, Thérèse M.F, Heppner Goss, Kathleen, Scott, M.Catherine, Witte, David P, Groden, Joanna, Cohen, Mitchell B
• Format: Article
• Language: English
• Subjects: Adenoma - genetics; Adenoma - pathology; adenomatous polyposis coli; Alleles; Animals; Colonic Neoplasms - genetics; Colonic Neoplasms - pathology; Disease Models, Animal; DNA Mutational Analysis; Down-Regulation; Epithelial Cells - metabolism; Epithelial Cells - pathology; Gastrointestinal Hormones; Gene Expression Regulation, Neoplastic; Genes, APC - genetics; Genes, APC - physiology; Genetic Predisposition to Disease - genetics; guanylate cyclase C; guanylin; Humans; In Situ Hybridization; Intestinal Neoplasms - genetics; Intestinal Neoplasms - pathology; Jejunum - metabolism; Mice; Mice, Inbred Strains; Mice, Mutant Strains; Min; multiple intestinal neoplasia; Mutation - genetics; Natriuretic Peptides; Peptides - genetics; Polymorphism, Genetic - genetics; Precancerous Conditions - genetics; Precancerous Conditions - pathology; RNA, Messenger - genetics; RNA, Messenger - metabolism; Species Specificity
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1006/bbrc.2000.2917

Guanylin is a pro-secretory hormone that is expressed in intestinal epithelia. Previously, we mapped the guanylin gene to mouse and human chromosomal regions containing multiple intestinal tumor-modifying loci. Here, we investigate whether guanylin expression is downregulated in precancerous human and mouse intestinal adenomas and whether diminished guanylin expression increases adenoma susceptibility in an animal model of intestinal cancer, the multiple intestinal neoplasia (Min) mouse. In situ hybridization analysis indicated diminished guanylin expression in both mouse and human adenomas. Northern analysis of mouse intestinal tissues showed strain-specific levels of guanylin expression but no correlation with the resistance or susceptibility 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 significant loss of guanylin RNA in adenomas of mouse and human is a marker of intestinal epithelial cell transformation.