Contribution of gastrin-releasing peptide and its receptor to villus development in the murine and human gastrointestinal tract.
Recent studies have shown that aberrantly expressed gastrin-releasing peptide (GRP) and its receptor (GRP-R) critically regulate tumor cell differentiation in colon cancers developing in humans and mice. This finding suggested that the ability of GRP/GRP-R to promote a well-differentiated phenotype in colon cancer might reflect a re-capitulation of a normal role in regulating intestinal organogenesis. To determine if this was the case, we compared and contrasted intestinal development in GRPR-/- mice with their wild type littermates. GRP/GRP-R co-expression in wild type mice was only observed in villous enterocytes between N-1 and N-12. During this time frame villous growth was completely attenuated in GRPR-/- mice. The contribution of GRP/GRP-R to villous growth was due to their act in increasing enterocyte proliferation prior to N-8 but increasing enterocyte size thereafter. From N-12 onwards, small intestinal villous growth in GRPR-/- mice resumed such that no difference in this structure could be detected at adulthood between mice of either genotype. We next studied GRP/GRP-R expression in human abortuses. These proteins were co-expressed by villous enterocytes only between weeks 14 and 20 post-conception, a time frame analogous to when they are expressed in the murine intestine. Thus, this study shows for the first time that GRP/GRP-R play a transient and non-critical role in intestinal development, yet provides a rationale for their re-appearance in colon cancer.
Carroll
Robert E
RE
Department of Medicine, University of Illinois at Chicago and Chicago Veterans Administration Medical Center (West Side Division), 840 South Wood Street (M/C 787), Chicago, IL 60612, USA.
Matkowskyj
Kristina
K
Saunthararajah
Yogen
Y
Sekosan
Marin
M
Battey
James F
JF
Benya
Richard V
RV
D037881:Aborted Fetus; D000818:Animals; D002455:Cell Division; D002469:Cell Separation; D004064:Digestive System / Q000196:embryology*; D020895:Enterocytes / Q000378:metabolism*; D005434:Flow Cytometry; D019886:Gastrin-Releasing Peptide / Q000096:biosynthesis / Q000502:physiology*; D005838:Genotype; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D010641:Phenotype; D018004:Receptors, Bombesin / Q000096:biosynthesis / Q000502:physiology*; D013997:Time Factors
D018004:Receptors, Bombesin; D019886:Gastrin-Releasing Peptide