Expression of guanylin is downregulated in mouse and human intestinal adenomas.
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.
Steinbrecher
K A
KA
Division of Pediatric Gastroenterology and Nutrition, Children's Hospital Medical Center, Cincinnati, Ohio 45229, USA.
Tuohy
T M
TM
Heppner Goss
K
K
Scott
M C
MC
Witte
D P
DP
Groden
J
J
Cohen
M B
MB
D000236:Adenoma / Q000235:genetics* / Q000473:pathology; D000483:Alleles; D000818:Animals; D003110:Colonic Neoplasms / Q000235:genetics / Q000473:pathology; D004252:DNA Mutational Analysis; D004195:Disease Models, Animal; D015536:Down-Regulation; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D005768:Gastrointestinal Hormones; D015972:Gene Expression Regulation, Neoplastic; D017491:Genes, APC / Q000235:genetics / Q000502:physiology; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D017403:In Situ Hybridization; D007414:Intestinal Neoplasms / Q000235:genetics* / Q000473:pathology; D007583:Jejunum / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D008817:Mice, Mutant Strains; D009154:Mutation / Q000235:genetics; D045265:Natriuretic Peptides; D010455:Peptides / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics; D011230:Precancerous Conditions / Q000235:genetics / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013045:Species Specificity
D005768:Gastrointestinal Hormones; D045265:Natriuretic Peptides; D010455:Peptides; D012333:RNA, Messenger; C072685:guanylin