Overexpression of glycine-extended gastrin in transgenic mice results in increased colonic proliferation

J Clin Invest. 1999 Apr;103(8):1119-26. doi: 10.1172/JCI4910.


Gastrin is a peptide hormone involved in the growth of both normal and malignant gastrointestinal tissue. Recent studies suggest that the glycine-extended biosynthetic intermediates mediate many of these trophic effects, but the in vivo relevance of glycine-extended gastrin (G-Gly) has not been tested. We have generated mice (MTI/G-GLY) that overexpress progastrin truncated at glycine-72 to evaluate the trophic effects of G-Gly in an in vivo model. MTI/G-GLY mice have elevated serum and colonic mucosal levels of G-Gly compared with wild-type mice. MTI/G-GLY mice had a 43% increase in colonic mucosal thickness and a 41% increase in the percentage of goblet cells per crypt. MTI/G-GLY mice exhibited increased colonic proliferation compared with wild-type controls, with an expansion of the proliferative zone into the upper third of the colonic crypts. Continuous infusion of G-Gly into gastrin-deficient mice for two weeks also resulted in elevated G-Gly levels, a 10% increase in colonic mucosal thickness, and an 81% increase in colonic proliferation when compared with gastrin-deficient mice that received saline alone. To our knowledge, these studies demonstrate for the first time that G-Gly's contribute to colonic mucosal proliferation in vivo.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cell Division
  • Colon / pathology*
  • Gastrins / genetics
  • Gastrins / physiology*
  • Gastrointestinal Neoplasms / prevention & control
  • Gene Expression
  • Glycine*
  • Goblet Cells / pathology
  • Humans
  • Hyperplasia / pathology
  • Hypertrophy / pathology
  • Male
  • Mice
  • Mice, Transgenic
  • Protein Precursors / genetics
  • Protein Precursors / physiology*
  • Stomach / pathology
  • Tumor Cells, Cultured


  • Gastrins
  • Protein Precursors
  • big gastrin
  • Glycine