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Guanylin
mRNA Expression in Human Intestine and Colorectal Adenocarcinoma |
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Mitchell B.
Cohen, Jennifer A. Hawkins, and David P. Witte |
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Division
of Pediatric Gastroenterology and Nutrition (MBC, JAH), Department of Pathology
(DPW), Children's Hospital Research Foundation, and University of Cincinnati,
Cincinnati, Ohio |
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Guanylin is a mammalian
peptide ligand that binds to the enterocyte receptor guanylyl cyclase C
and mediates Cl- and HCO3- efflux via the cystic fibrosis transmembrane
conductance regulator. To identify the regional localization of guanylin
mRNA in the human intestine, we performed in situ hybridization using a
guanylin-specific riboprobe. The pattern of guanylin mRNA distribution is
complex and includes all epithelial lineages at various points along the
duodenal-to-colonic axis. Guanylin mRNA expression is most prominent in
the distal small intestine and colon. In the normal colon, guanylin mRNA
is robustly expressed in superficial epithelial cells; in colorectal adenocarcinoma,
however, guanylin mRNA expression is absent. Guanylin mRNA is detectable
in several intestinal tumor cell lines, although at much lower levels than
those seen in the human intestine. The pattern of guanylin expression is
consistent with the possibility of region-specific functions for guanylin
within the human intestine. Furthermore, the diminished expression 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 guanylin activity leads to
or is a result of adenocarcinoma formation. |
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