Mice overexpressing progastrin are predisposed for developing aberrant colonic crypt loci in response to AOM

Pomila Singh, Marco Velasco, Randall Given, Michael Wargovich, Andrea Varro, Timothy C. Wang

Research output: Contribution to journalArticle

73 Citations (Scopus)

Abstract

Recent studies show that nonamidated gastrins (Gly-gastrin and progastrin) stimulate colonic proliferation. However, the role of nonamidated vs. amidated gastrins in colon carcinogenesis has not been defined. We measured intermediate markers of carcinogenesis in transgenic mice overexpressing either progastrin (hGAS) or amidated gastrin (INS-GAS) in response to azoxymethane (AOM). The hGAS mice showed significantly higher numbers of aberrant crypt foci (140200% increase) compared with that in wild- type (WT) and INS-GAS mice (P < 0.05) after AOM treatment. The bromodeoxyuridine-labeling index of colonic crypts also was significantly elevated in hGAS mice vs. that in WT and INS-GAS mice. The results therefore provide evidence for a mitogenic and cocarcinogenic role of nonamidated gastrins (progastrin), which is apparently not shared by the amidated gastrins. Although nonamidated gastrins are now believed to mediate mitogenic effects via novel receptors, amidated gastrins media ate biological effects via different receptor subtypes, which may explain the difference in the cocarcinogenic potential of nonamidated vs. amidated gastrins. In conclusion, our results provide strong support for a cocarcinogenic role for nonamidated gastrins in colon carcinogenesis.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume278
Issue number3 41-3
StatePublished - Mar 2000

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Azoxymethane
Gastrins
Carcinogenesis
Colon
Aberrant Crypt Foci
Cholecystokinin B Receptor
big gastrin
Bromodeoxyuridine
Transgenic Mice

Keywords

  • Transgenic mice

ASJC Scopus subject areas

  • Gastroenterology
  • Physiology
  • Physiology (medical)

Cite this

Mice overexpressing progastrin are predisposed for developing aberrant colonic crypt loci in response to AOM. / Singh, Pomila; Velasco, Marco; Given, Randall; Wargovich, Michael; Varro, Andrea; Wang, Timothy C.

In: American Journal of Physiology - Gastrointestinal and Liver Physiology, Vol. 278, No. 3 41-3, 03.2000.

Research output: Contribution to journalArticle

Singh, Pomila ; Velasco, Marco ; Given, Randall ; Wargovich, Michael ; Varro, Andrea ; Wang, Timothy C. / Mice overexpressing progastrin are predisposed for developing aberrant colonic crypt loci in response to AOM. In: American Journal of Physiology - Gastrointestinal and Liver Physiology. 2000 ; Vol. 278, No. 3 41-3.
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