GUANYLIN MESSENGER-RNA EXPRESSION IN HUMAN INTESTINE AND COLORECTAL ADENOCARCINOMA

Guanylin is a mammalian peptide ligand that binds to the enterocyte re ceptor guanylyl cyclase C and mediates Cl- and HCO3- efflux via the cy stic fibrosis transmembrane conductance regulator. To identify the reg ional localization of guanylin mRNA in the human intestine, we perform ed in situ hybridization using a guanylin-specific riboprobe. The patt ern of guanylin mRNA distribution is complex and includes all epitheli al lineages at various points along the duodenal-to-colonic axis. Guan ylin mRNA expression is most prominent in the distal small intestine a nd colon. In the normal colon, guanylin mRNA is robustly expressed in superficial epithelial cells; in colorectal adenocarcinoma, however, g uanylin mRNA expression is absent. Guanylin mRNA is detectable in seve ral intestinal tumor cell lines, although at much lower levels than th ose seen in the human intestine. The pattern of guanylin expression is consistent with the possibility of region-specific functions for guan ylin within the human intestine. Furthermore, the diminished expressio n of guanylin mRNA in adenocarcinoma of the colon and in colon cancer cell lines, along with the chromosomal localization of guanylin to the tumor modifier region 1p34-35, raises the possibility that loss of gu anylin activity leads to or is a result of adenocarcinoma formation.