gastrins and Aberrant-Crypt-Foci

Transgenic mice overexpressing human progastrin (hGAS) show colonic crypt hyper-proliferation and elevated susceptibility to colon carcinogenesis. We aimed to investigate effects of p53 mutation on colon carcinogenesis in hGAS mice. We show that introducing a p53 gene mutation further increases progastrin dependent BrdU labeling and results in markedly elevated number of aberrant crypt foci (ACF) and colonic tumors. We demonstrate that hGAS/Lgr5-GFP mice have higher number of Lgr5+ colonic stem cells per crypt when compared to Lgr5-GFP mice indicating that progastrin changes crypt biology through increased stem cell numbers and additional p53 mutation leads to more aggressive phenotype in this murine colon cancer model.

Topics: Aberrant Crypt Foci; Animals; Azoxymethane; Carcinogens; Cell Proliferation; Cell Transformation, Neoplastic; Colonic Neoplasms; Disease Models, Animal; Female; Gastrins; Humans; Immunohistochemistry; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Mutation; Protein Precursors; Tumor Suppressor Protein p53